Effect of Catechol-O-Methyltransferase Genotype on Self-Reported Efficacy and Activity Changes in the Brain Prefrontal Area in Response to a Caffeine Placebo / 医薬品情報学

Objective: The placebo effect can enhance the response to treatment, even in the absence of pharmacological ingredients. One possible factor explaining the likelihood of the placebo effect in individuals is genetic polymorphisms in neurotransmitters. This study focused on gene polymorphisms in the catechol-O-methyltransferase (COMT) as an interindividual variable of the placebo effect.Design・Methods: All 120 participants were explained the effects of caffeine, including its ability to ameliorate drowsiness and increase concentration, and then given a placebo (lactose). The onset of the placebo effect was measured in terms of the degree of caffeine-reduced sleepiness using subjective indices of the Stanford Sleepiness Scale (SSS) and a feeling of drowsiness-Visual Analogue Scale (VAS). The mechanism of the placebo effect was objectively examined in terms of changes in cerebral blood flow in the prefrontal cortex of the brain. In addition, we investigated participants’ susceptibility to the placebo effect by examining genetic polymorphisms in COMT.Results: After taking the drug, sleepiness on the SSS and VAS was significantly improved (p＜0.001), although there was no change in prefrontal cortex activity. Among the 120 participants, 63 had a Val/Val-type polymorphism in COMT (52.5%), 45 had a Val/Met-type (37.5%), and 12 had a Met/Met-type (10.0%). There were no significant differences among COMT gene polymorphisms in the subjective measures of SSS and VAS. However, there was a tendency for the cerebral blood flow changes to be larger in the left hemisphere of the brain in individuals with the Met/Met type.Conclusion: There seems to be a relationship between prefrontal cortex activity and genetic polymorphisms. In particular, there may be a correlation between the expression of a placebo effect and COMT gene polymorphisms.

Polimorfismo genético associado a doença renal crônica e periodontite: uma revisão sistemática de literatura / Genetic polymorphism associated with chronic kidney disease and periodontitis: a systematic literature review / Polimorfismo genético asociado a enfermedad renal crónica y periodontitis: una revisión sistemática de la literatura

A periodontite é uma doença infecto-inflamatória associada ao biofilme disbiótico que afeta os tecidos de proteção e de suporte dos dentes. O processo inflamatório que ocorre durante a periodontite tem sido associado à inflamação sistêmica em pacientes com doença renal crônica. Os polimorfismos genéticos são alterações no DNA que podem ter classificações diferentes dependendo da mutação gerada, e podem ser criados ou destruídos. Objetivo: O objetivo desta revisão sistemática da literatura foi elucidar a seguinte questão: os polimorfismos genéticos estão associados à doença renal crônica e à periodontite? Material e Métodos: A pesquisa foi realizada no PubMed, Biblioteca Cochrane, EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Bibliografia Brasileira de Odontologia (BBO), Biblioteca Virtual em Saúde (BVS), SciELO, Scopus, Web of Science e bases de dados de literatura cinzenta (Google Scholar) sem restrições de data ou idioma em 28 de junho de 2021 e atualizada em 26 de janeiro de 2023. Os descritores padronizados (Medical Subject Headings, MeSH) utilizados foram: "polimorfismo genético", "doença renal crônica" e "periodontite", de acordo com o banco de dados consultado, utilizando os operadores booleanos "AND". Resultado: 25 publicações foram identificadas. Após a análise do título, do resumo e do texto completo, 6 estudos de caso-controle foram selecionados para análise. Todos incluíam artigos investigando o papel de diferentes polimorfismos genéticos em ambas as doenças. Alguns genes apresentavam uma relação próxima com o perfil inflamatório que caracteriza ambas as doenças. Conclusão: Entre os polimorfismos estudados, os polimorfismos VNTR no gene IL4 e MCP-1-2518 A/G apresentaram uma associação positiva tanto com a periodontite quanto com a doença renal crônica. Entretanto, são necessários mais estudos para melhor compreensão do papel dos polimorfismos genéticos nessas doenças.

Periodontitis is an infectious-inflammatory disease associated with dysbiotic biofilm that affects the protective and supporting tissues of the teeth. The inflammatory process that occurs during periodontitis has been associated with systemic inflammation in patients with chronic kidney disease. Genetic polymorphisms are changes in DNA that can have different classifications depending on the mutation generated, and can be created or destroyed. Objective: The aim of this systematic review of the literature was to elucidate the following question: are genetic polymorphisms associated with chronic kidney disease and periodontitis? Material and Methods: The search was conducted in PubMed, Cochrane Library, EMBASE, Latin American and Caribbean Literature on Health Sciences (LILACS), Brazilian Bibliography of Dentistry (BBO), Virtual Health Library (VHL), SciELO, Scopus, Web of Science and gray literature databases (Google Scholar) without date or language restrictions on June 28, 2021 and updated on January 26, 2023. The standardized descriptors (Medical Subject Headings, MeSH) used were: "genetic polymorphism", "chronic kidney disease" and "periodontitis", according to the database consulted, using the Boolean operators "AND". Result: 25 publications were identified. After reviewing the title, abstract, and full text, 6 case-control studies were selected for analysis. All included articles investigating the role of different genetic polymorphisms in both diseases. Some genes showed a close relationship with the inflammatory profile that characterizes both diseases. Conclusion: Among the polymorphisms studied, the VNTR polymorphisms in the IL4 gene and MCP- 1-2518 A/G showed a positive association with both periodontitis and chronic kidney disease. However, further studies are needed to better understand the role of genetic polymorphisms in these diseases.

La periodontitis es una enfermedad infeccioso-inflamatoria asociada a un biofilm disbiótico que afecta a los tejidos protectores y de soporte de los dientes. El proceso inflamatorio que se produce durante la periodontitis se ha asociado con la inflamación sistémica en pacientes con enfermedad renal crónica. Los polimorfismos genéticos son cambios en el ADN que pueden tener diferentes clasificaciones dependiendo de la mutación generada, pudiendo ser creados o destruidos. Objetivo: El objetivo de esta revisión sistemática de la literatura fue dilucidar la siguiente pregunta: ¿están asociados los polimorfismos genéticos con la enfermedad renal crónica y la periodontitis? Material y Métodos: La búsqueda fue realizada en PubMed, Cochrane Library, EMBASE, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Bibliografía Brasileña de Odontología (BBO), Biblioteca Virtual en Salud (BVS), SciELO, Scopus, Web of Science y bases de datos de literatura gris (Google Scholar) sin restricciones de fecha o idioma el 28 de junio de 2021 y actualizada el 26 de enero de 2023. Los descriptores normalizados (Medical Subject Headings, MeSH) utilizados fueron: "polimorfismo genético", "enfermedad renal crónica" y "periodontitis", según la base de datos consultada, utilizando los operadores booleanos "AND". Resultado: Se identificaron 25 publicaciones. Tras analizar el título, el resumen y el texto completo, se seleccionaron 6 estudios de casos y controles para su análisis. Todos los trabajos incluidos investigaban el papel de diferentes polimorfismos genéticos en ambas enfermedades. Algunos genes mostraron una estrecha relación con el perfil inflamatorio que caracteriza a ambas enfermedades. Conclusión: Entre los polimorfismos estudiados, los polimorfismos VNTR en el gen IL4 y MCP-1-2518 A/G mostraron una asociación positiva tanto con la periodontitis como con la enfermedad renal crónica. Sin embargo, se necesitan más estudios para comprender mejor el papel de los polimorfismos genéticos en estas enfermedades.

Polimorfismos genéticos implicados en el desarrollo de la purpura trombocitopénica inmune / Genetic polymorphisms involved in the development of Immune Thrombocytopenic Purpura

Introducción: los cambios en el ácido desoxirribonucleico se conocen como mutaciones, estas dan lugar a los polimorfismos, los cuales generan variación alélica entre individuos y diversidad de la misma especie. Se ha sugerido que los polimorfismos genéticos en los mediadores inmunitarios desempeñan un papel fundamental en la patogénesis de muchos trastornos autoinmunes, como en la púrpura trombocitopénica inmune, siendo esta el tipo más común de púrpura trombocitopénica y, a menudo, se diagnostica como un tipo de trastorno autoinmune, debido a la destrucción de las plaquetas mediadas por el sistema inmunitario. Objetivo: realizar una revisión bibliográfica sobre el papel de los polimorfismos genéticos y su influencia en el desarrollo de la púrpura trombocitopénica inmune. Métodos: se realizó revisión literaria en inglés y español en PubMed y Elsevier, desde marzo hasta mayo del 2021, con el uso de combinación de palabras clave y términos MeSH, como púrpura trombocitopénica y polimorfismos genéticos. Se realizó análisis y resumen de la literatura encontrada. Conclusión: la púrpura trombocitopénica inmune es considerada como una patología multifactorial, causada por factores ambientales y genéticos, dentro de los cuales se encuentran los polimorfismos para los mediadores inmunitarios que pueden llevar a una exacerbación de la enfermedad o no intervenir en la misma.

Introduction: Changes in deoxyribonucleic acid are known as mutations, these give place to polymorphisms, which generate allelic variation between individuals and provide diversity among same species. Genetic polymorphisms in immune mediators have been suggested to play a key role in the pathogenesis of many autoimmune disorders, such as immune thrombocytopenic purpura, this being the most common type of thrombocytopenic purpura and is often diagnosed as a type of autoimmune disorder, due to the destruction of platelets mediated by the immune system. Objective: To execute a bibliographic review on the role of genetic polymorphisms and their influence on the development of immune thrombocytopenic purpura. Methods: A literary review in English and Spanish was performed in PubMed and Elsevier from March to May 2021, with the use of a combination of keywords and MeSH terms such as Thrombocytopenic Purpura and genetic polymorphisms. Analysis and summary of the literature found was executed. Conclusion: Immune thrombocytopenic purpura is considered a multifactorial pathology, caused by environmental and genetic factors, among which are polymorphisms for immune mediators that can lead to an exacerbation of the disease or not intervene in the same.

Por trás da leptina: uma revisão de literatura / Behind the leptin: a literature review / Detrás de leptin: una revisión de la literatura

A obesidade é uma doença crônica, multifatorial, que afeta todas as idades e classes sociais. Esta comorbidade tem avançado em decorrência de diversos fatores e sua prevalência está ancorada em diferentes dimensões como as biológicas, sociais, históricas, comportamentais, saúde pública e política. O presente estudo tem como objetivo caracterizar o gene da leptina, seu produto e de seus receptores, assim como os mecanismos que corroboram com o desenvolvimento da obesidade e seu envolvimento com distúrbios alimentares. A leptina é uma proteína secretada principalmente nos adipócitos, ela reduz o apetite por meio da inibição da formação de neuropeptídeos relacionados ao apetite, como o neuropeptídeo Y e eleva a expressão de neuropeptídeos anorexígenos, como o hormônio liberador de corticotropina, por isso que os altos níveis de leptina reduzem a ingestão alimentar, em contraste com os níveis baixos que induzem hiperfagia. Como a leptina realiza o controle da saciedade e regulação do gasto energético, o indivíduo com disfunção neste gene não desenvolve essa função corretamente. Isso se deve aos SNPs, que de acordo com estudos aumentam a susceptibilidade à obesidade. Além do mais, a leptina pode estar envolvida com processo patológico de alguns distúrbios alimentares, predispondo o paciente às condições como anorexia nervosa e bulimia.

Obesity is a chronic, multifactorial disease that affects all ages and social classes. This comorbidity has advanced as a result of several factors and its prevalence is anchored in different dimensions such as biological, social, historical, behavioral, public health and political. The present study aims to characterize the leptin gene, its product and its receptors, as well as the mechanisms that corroborate the development of obesity and its involvement with eating disorders. Leptin is a protein secreted mainly in adipocytes, it reduces appetite by inhibiting the formation of appetite-related neuropeptides such as neuropeptide Y and elevates the expression of anorexic neuropeptides such as corticotropin-releasing hormone, so high levels of leptin reduce dietary intake, in contrast to low levels that induce hyperphagia. As leptin performs satiety control and regulation of energy expenditure, the individual with dysfunction in this gene does not develop this function properly. This is due to SNPs, which according to studies increase susceptibility to obesity. Furthermore, leptin may be involved with the pathological process of some eating disorders, predisposing the patient to conditions such as anorexia nervosa and bulimia.

La obesidad es una enfermedad crónica multifactorial que afecta a todas las edades y clases sociales. Esta comorbilidad ha avanzado como resultado de diversos factores y su prevalencia está anclada en diferentes dimensiones, como la biológica, la social, la histórica, la conductual, la salud pública y la política. El objetivo de este estudio es caracterizar el gen de la leptina, su producto y sus receptores, así como los mecanismos que corroboran el desarrollo de la obesidad y su participación en los trastornos alimentarios. La leptina es una proteína secretada principalmente en los adipocitos, reduce el apetito inhibiendo la formación de neuropéptidos relacionados con el apetito, como el neuropéptido Y y eleva la expresión de neuropéptidos anorexógenos, como la hormona que libera la corticotropina, razón por la cual los altos niveles de leptina reducen la ingesta dietética, en contraste con los bajos niveles inducir hiperagia. Como la leptina lleva a cabo el control de la saciedad y la regulación del gasto energético, el individuo con disfunción en este gen no desarrolla esta función correctamente. Esto se debe a los SNP, que según los estudios aumentan la susceptibilidad a la obesidad. Además, la leptina puede estar implicada en el proceso patológico de algunos trastornos alimentarios, predisponiéndose al paciente a condiciones tales como anorexia nerviosa y bulimia.

TP53 and p21 (CDKN1A) polymorphisms and the risk of systemic lupus erythematosus

Abstract Background The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C—rs1042522; p53 PIN3—rs17878362; p21 31 C > A—rs1801270; p21 70 C > T—rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. Methods Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. Results Protective effect was observed for the genotype combinations p53 PIN3 A1/A1 -p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). Conclusions Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients. Highlights The polymorphisms TP53 rs1042522 (G > C) and TP53 rs17878362 (16 bp Del/Ins) were associated with SLE risk in whites. In whites, the combined genotype TP53 rs1042522 GC- TP53 rs17878362 A1A2 and the haplotype TP53 rs1042522 C-rs17878362 A2 represented higher SLE risk. Combination of TP53 rs17878362 (16 bp Del/Ins) and p21 rs1801270 (C > A) protected against SLE in non-white women. TP53 and p21 (CDKN1A) polymorphisms may be SLE susceptibility markers for specific groups.

Genetic variability in the neurobiology of nicotine dependence: effects on smoking behavior / A variabilidade genética na neurobiologia da adição à nicotina: reflexos no comportamento tabágico

Abstract Background Smoking dependence is a chronic disease and a public health problem. The neurobiology of nicotine addiction can explain smoking behavior. This system has genetic variability that has been associated with vulnerability to dependence. Genetic variability in the neurobiology of smoking can help to understand why individuals exposed to drugs may or may not become addicted. Objective This study aims to address genetic variability in the neurobiology of smoking addiction with a focus on polymorphic genes related to the nicotinic response and the dopaminergic reward pathway. Method This work involved a search of the main scientific research on genetic variability in the neurobiology of smoking and its effects on smoking behavior. One hundred and five studies were selected, most of which highlighted polymorphisms in the genes of nicotinic receptors, dopamine receptors, and nicotine metabolism. Results The majority of studies have focused on genes related to the activation of the dopaminergic reward system by nicotine. Combinations between different polymorphisms were also highlighted, showing that interactions can determine a genetic profile of predisposition to smoking addiction. Additionally, gender and ethnicity were identified as relevant factors. Conclusion Knowledge of the genetic bases involved in the individual response to smoking can enable a better understanding of inter-individual differences in smoking behavior, and contribute to improving the treatment of addiction.

Resumo Introdução A dependência nicotínica é uma doença crônica e um problema de saúde pública. O comportamento tabágico pode ser explicado pela neurobiologia da adição, cujas variações genéticas têm sido associadas à dependência. A variabilidade genética na neurobiologia do tabagismo pode ajudar a entender por que indivíduos expostos a drogas podem ou não se tornar viciados. Objetivo Este estudo tem como objetivo abordar a variabilidade genética na neurobiologia do tabagismo com foco em genes polimórficos relacionados à resposta nicotínica e à via de recompensa dopaminérgica. Método Uma pesquisa foi realizada nas principais bases de dados científicos sobre a variabilidade genética na neurobiologia do tabagismo e seus efeitos no comportamento do tabagismo. 105 estudos foram selecionados, em sua maioria destacando polimorfismos nos genes de receptores nicotínicos, receptores de dopamina e de metabolismo da nicotina. Resultados A maioria dos estudos concentrou-se em genes relacionados à ativação do sistema de recompensa dopaminérgico pela nicotina. Determinadas combinações entre genótipos de diferentes polimorfismos também se destacaram, mostrando que interações gênicas podem determinar um perfil genético de predisposição ao tabagismo. Além disso, gênero e etnia foram identificados como fatores relevantes. Conclusão O conhecimento das bases genéticas envolvidas na resposta individual ao tabagismo pode permitir uma melhor compreensão das diferenças interindividuais no comportamento tabágico e contribuir para melhoria dos tratamentos disponíveis para a dependência.

Variability of PDYN and OPRK1 genes in four argentinian populations and its genetic association with clinical variables related to acute postsurgical pain / Variabilidad de los genes PDYN y OPRK1 en cuatro poblaciones argentinas y su asociación con variables clínicas relacionadas al dolor agudo post-quirúrgico

ABSTRACT Several population studies showed an association between variation in pain sensitivity and genetic polymorphisms located in Prodynorphin (PDYN) and Kappa Opioid Receptor (OPRK1) human genes. We analysed polymorphisms of these two genes to characterise their variation in Argentinian populations, as well as to evaluate their association with acute pain sensitivity. We studied 11 genetic markers in individuals from four locations in Argentina (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, and Misión Nueva Pompeya), calculated the population parameters, and evaluated the possible association among pain sensitivity, clinical, and genetic variables through a Generalised Estimating Equation model. High linkage disequilibrium was observed in the four populations for both genes, and significant differences were found among frequencies of Argentinian populations and those from other continents reported in the 1000 Genomes Project. Four PDYN gene polymorphisms from 3´ untranslated region and exon 4 showed association with acute pain sensitivity. One genotype of each of these polymorphisms was associated with a higher pain sensitivity, probably related with the activation of the N-methyl-D-aspartate (NMDA) receptors. We found a strong association with acute pain for the following clinical variables: 1) time after surgery, 2) intravenous klosidol supplied every 8 h, and 3) type of incision. Our results highlight the importance of a regional study of genetic variants which influence pain sensitivity and analgesic response.

RESUMEN La asociación entre la sensibilidad al dolor y los polimorfismos que presentan los genes humanos de prodinorfina (PDYN) y receptor opioide kappa (OPRK1) se ha evidenciado en distintos estudios poblacionales. Con el objetivo de caracterizar la variación de estos genes y evaluar su asociación con dolor agudo en la población argentina, analizamos 11 polimorfismos en individuos provenientes de cuatro localidades argentinas (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, y Misión Nueva Pompeya). Calculamos los parámetros poblacionales y evaluamos la posible asociación entre sensibilidad al dolor, variables clínicas y variables genéticas a través de un modelo de ecuación generalizada de estimación. Se observó alto desequilibrio de ligamiento para ambos genes en las cuatro poblaciones analizadas, y se encontraron diferencias significativas entre las frecuencias de poblaciones argentinas y las reportadas en el Proyecto 1000 Genomes para poblaciones de otros continentes. Cuatro polimorfismos de la región 3´UTR y el exón 4 de PDYN mostraron asociación con la sensibilidad al dolor agudo. En cada uno de estos polimorfismos, un genotipo resultó asociado con alta sensibilidad al dolor, probablemente en relación con la activación de receptores N-metil-D-aspartato (NMDA). Encontramos una fuerte asociación con dolor agudo para las siguientes variables clínicas: 1) tiempo post-cirugía, 2) administración intravenosa de klosidol cada 8 h, y 3) tipo de incisión. Nuestros resultados resaltan la importancia de realizar estudios regionales de variables genéticas que influyen en la sensibilidad al dolor y la respuesta analgésica.

Estudo de associação entre polimorfismos genéticos e níveis plasmáticos do VEGF, FLT1, KDR e o risco para depressão / Study of association between genetic polymorphisms and plasma levels of VEGF, FLT1, KDR and the risk for depression

Introdução: a depressão é um transtorno mental comum, grave e incapacitante que afeta mais de 350 milhões de pessoas em todo o mundo. A depressão é caracterizada principalmente por sintomas como tristeza, perda de interesse, diminuição da energia, perda de confiança e autoestima, culpa inadequada, distúrbios do sono e do apetite, pensamentos de morte e suicídio. Além disso, essa patologia também tem um forte impacto na qualidade de vida dos indivíduos afetados e de suas famílias. Sabe-se que fatores genéticos interagem com as condições socioambientais de modo a influenciar a predisposição das pessoas ao adoecimento. Estudos identificaram polimorfismos de nucleotídeos simples (SNPs) que podem ser marcadores genéticos apropriados para prever inflamação sistêmica, por exemplo, e a atual tese teve como foco o efeito de SNPs na via do fator de crescimento endotelial vascular (VEGF). Esta proteína é uma potente molécula angiogênica e está envolvida na neurogênese do hipocampo, uma das principais estruturas límbicas afetadas em pessoas com depressão. O VEGF está implicado em uma das principais teorias que tentam explicar a fisiopatologia deste transtorno mental grave, a teoria neurotrófica, a qual diz que a diminuição ou desregulação da sinalização de neurotrofinas pode contribuir para a manifestação do transtorno depressivo (TD). Objetivo: avaliar se polimorfismos do VEGF e seus receptores, KDR e FLT1, estão associados à depressão e à gravidade dos sintomas, à ideação e tentativas de suicídio, independentemente tanto de um tratamento otimizado quanto da presença de estresse precoce (do inglês, early-life stress, ELS), também verificar se há efeito destes polimorfismos nas concentrações plasmáticas de proteínas expressas pelos seus respectivos genes e observar se existe correlação entre VEGF e seus inibidores, VEGF e s100ß. Metodologia: participaram do presente estudo 160 pacientes com depressão e 114 controles saudáveis. Foram aplicados durante entrevista questionários que avaliaram o perfil clínico dos pacientes como o MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI e foi registrado o número de tentativas de suicídio. Os controles passaram por uma entrevista para serem avaliados quanto aos critérios de inclusão e exclusão do grupo. A genotipagem dos participantes foi realizada através da técnica de Real Time PCR e as mensurações de proteínas por meio do ensaio ensaio imunoenzimático (ELISA). Resultados: indivíduos com depressão, homozigotos AA do polimorfismo rs699947, apresentaram maiores concentrações plasmáticas de VEGF (P-valor= 0.006) e se associaram a um maior número de tentativas de suicídio na análise direta (P-valor= 0.041) e na análise corrigida foi observada uma tendência para a confirmação deste resultado (P-valor= 0.076). O genótipo homozigoto GG do polimorfismo rs7993418 do FLT1 se associou à severidade de sintomas (P-valor= 0.040), bem como uma tendência de associação com um aumento nas tentativas de suicídio e uma maior pontuação na escala que avaliou ideação suicida. Entre os pacientes quanto maior foram as concentrações plasmáticas de VEGF, maior foram as de KDR, FLT1 e s100ß. Conclusão: os resultados sugerem que os polimorfismos da via VEGF estão associados ao número de tentativas de suicídio e severidade dos sintomas depressivos

Introduction: Depression is a common, serious, and disabling mental disorder that affects more than 350 million people worldwide. Depression is mainly characterized by symptoms such as sadness, loss of interest, decreased energy, loss of confidence and self-esteem, inadequate guilt, sleep and appetite disturbances, thoughts of death and suicide. Furthermore, this pathology also has a strong impact on the quality of life of those affected and their families. It is known that genetic factors interact with social and environmental conditions to influence people's predisposition to illness. Studies have identified single nucleotide polymorphisms (SNPs) that may be appropriate genetic markers to predict systemic inflammation, for example, and the current thesis focused on the effect of SNPs on the vascular endothelial growth factor (VEGF) pathway. This protein is a potent angiogenic molecule and is involved in hippocampal neurogenesis, one of the main limbic structures affected in people with depression. VEGF is implicated in one of the main theories that try to explain the pathophysiology of this severe mental disorder, the neurotrophic theory, which says that the decrease or dysregulation of neurotrophin signaling can contribute to the manifestation of depressive disorder (DT). Objective: to assess whether polymorphisms of VEGF and its receptors, KDR and FLT1, are associated with depression and severity of symptoms, suicide ideation and attempts, regardless of both optimal treatment and the presence of early-life stress (ELS) in these associations. also check whether there is an effect of these polymorphisms on the plasma concentrations of proteins expressed by their respective genes and observe whether there is a correlation between VEGF and its inhibitors, VEGF and s100ß. Methodology: 160 patients with depression and 114 healthy controls participated in this study. Questionnaires that assessed the clinical profile of patients, such as the MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI, were applied during interviews, and the number of suicide attempts was recorded. The controls underwent an interview to be evaluated regarding the inclusion and exclusion criteria. The genotyping of the participants was performed using the Real Time PCR technique and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). Results: individuals with depression, homozygous AA of the rs699947 polymorphism, had higher plasma concentrations of VEGF (P-value = 0.006) and a greater number of suicide attempts in the direct analysis (P-value = 0.041) and in the corrected analysis a trend towards confirmation of this result was observed (P-value = 0.076). The GG genotype of the FLT1 polymorphism rs7993418 was associated with symptom severity (P-value = 0.040), as well as with a trend for association with increase in suicide attempts and a higher score on the scale that evaluated suicidal ideation. The bigger the plasma concentrations of VEGF, the higher were those of KDR, FLT1 and s100ß. Conclusion: the results indicate that VEGF pathway polymorphisms are associated with the number of suicides and severity of depressive symptoms

The role of pharmacogenomics in the personalization of Parkinson′s disease treatment / 中华神经科杂志

Parkinson′s disease (PD) is a common neurodegenerative disorder, which has a highly effective pharmacological symptomatic treatment. Levodopa is the most effective drug available for the symptomatic treatment of PD and is the gold standard with which other therapies must be compared. There are significant individual differences in clinical features, disease course, and response to pharmacological treatment in PD patients, not only attributed to disease process and environmental factors, but also genetic factors. Pharmacogenomics, also known as personalized medicine, is the study of how genetic variations in a person′s genome affect their response to drug therapies, which contribute to apply the patient with the best treatment plan, including the timing of dosing, the dose administered, and the most appropriate drugs. Pharmacogenomics accounts for 60%-90% variability in drug pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. This article will summarize the impact of polymorphisms in genes encoding dopamine signaling pathway on drug response, and the impact of genetic polymorphisms on complications and prognosis associated with dopaminergic drug therapy.

Risk factors for recurrent aphthous stomatitis: a systematic review / Factores de riesgo para la estomatitis aftosa recurrente: revisión sistemática

SUMMARY: The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

RESUMEN: Aún se desconoce la causa y cómo prevenir la estomatitis aftosa recurrente (más conocida como aftas). En esta revisión sistemática (registro PROSPERO #CRD42019122214) mostramos que la mayoría de los factores de riesgo para la enfermedad son polimorfismos genéticos de un solo nucleótido en genes relacionados con el funcionamiento del sistema inmune (TLR4, MMP9, E- selectin, IL-1 beta y TNF-alfa). Los polimorfismos genéticos de un solo nucleótido no constituyen un riesgo modificable.Ello indica que, al menos en parte, la susceptibilidad para las aftas es hereditaria y que esos factores no pueden ser modificados.

Genetic markers for preeclampsia in Peruvian women / Marcadores genéticos de preeclampsia en mujeres peruanas

Abstract Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Resumen Antecedentes: La preeclampsia es un trastorno multiorgánico asociado con la morbi-mortalidad materna y perinatal. En el Perú, su incidencia es del 10% y causa el 22% de las muertes maternas. Se encontró una asociación entre la preeclampsia y ciertos polimorfismos. Objetivo: Determinar asociación entre los polimorfismos genéticos del factor de crecimiento endotelial vascular (VEGF) +936 C/T y +405 G/C, interleucina-6 (IL-6) -174G/C, IL-1β -511 C/T, Apo A-1 -75 G/A, Apo B-100 2488 C/T (Xbal), y preeclampsia en gestantes peruanas. Métodos: Se incluyeron gestantes preeclámpticas y sanas (controles). Las muestras de sangre fueron procesadas para extracción del ADN, y el análisis se realizó con la técnica PCR-RFLP con protocolos específicos para cada gen y confirmación con secuenciamiento Sanger. Se compararon las frecuencias alélicas y genotípicas en los casos (preeclampsia) y los controles. Resultados: No se halló asociación entre los polimorfismos VEGF+936-C/T y VEGF+405 y la preeclampsia. Las frecuencias de los genotipos GG y el alelo G del polimorfismo -174-G/C en el gen IL6 en preeclámpticas y controles, mostraron diferencias significativas, con frecuencias más altas en los casos. Para el polimorfismo -511-C/T del gen IL-1β, no se encontraron diferencias significativas en las frecuencias de genotipos TT comparados con CT+CC. Los genotipos y alelos de las variantes Apo-A1-75-G/A y Apo-B100 Xbal no mostraron diferencias significativas entre los grupos Conclusión: No se encontró asociación entre los marcadores genéticos estudiados y la preeclampsia. Sin embargo, el polimorfismo -174-G/C en el gen IL6 mostró diferencias significativas principalmente en el genotipo GG y el alelo G.

Influência de polimorfismos nos genes antioxidantes GSTM1, GSTT1 e GSTP1 no desenvolvimento de complicações oftalmológicas em diabéticos tipo 2 / Influence of polymorphisms in the GSTM1, GSTT1, and GSTP1 antioxidant genes on the development of ophthalmic complications in persons with type 2 diabetes

Introdução: A diabetes tipo 2 (DM2) é uma desordem metabólica ocasionada pela disfunção das células beta pancreáticas que interferem na produção de insulina e/ou pela resistência dos órgãos alvos a esse hormônio. Níveis elevados de radicais livres em conjunto com o declínio das defesas antioxidantes presente na DM2 podem ocasionar danos a organelas celulares, promovendo complicações da doença. As glutationas S- transferases (GST) são as principais enzimas antioxidantes que participam da defesa celular contra o estresse oxidativo. Os polimorfismos nos genes que codificam essas enzimas podem acarretar o surgimento de complicações oftalmológicas em diabéticos. Este trabalho avaliou a influência dos polimorfismos nos genes GST no desenvolvimento de doenças como a catarata e o glaucoma em pacientes com DM2 na Grande Vitória (ES). Metodologia: Os polimorfismos dos genes GSTM1 e GSTT1 foram investigados através da técnica de PCR multiplex. Para o gene GSTP1 utilizou-se a técnica PCR- RFLP. A análise estatística foi realizada através do teste exato de Fisher ou do teste do qui-quadrado com P-valor < 0.05. Resultados: Não foi encontrada relação entre os polimorfismos nos genes GSTM1, GSTT1 e GSTP1 e o surgimento de doenças como glaucoma e catarata em pacientes com DM2. Conclusão: Nossos dados sugerem que os polimorfismos nulos nos genes GSTM1 e GSTT1 e o polimorfismo Ile105Val no gene GSTP1 não estão associados com a suscetibilidade individual para o desenvolvimento de complicações oftalmológicas em pacientes com DM2. (AU)

Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by beta cell dysfunction that interferes with insulin production and/or by the resistance of target organs to this hormone. An increase in free radicals together with a decline in antioxidant defenses, present in T2DM, can damage cellular organelles and promote the occurrence of disease complications. Glutathione S-transferases (GSTs) are the main antioxidant enzymes involved in cellular defense against oxidative stress, and polymorphisms in genes encoding GSTs can lead to ophthalmic complications in persons with diabetes. In this study, we evaluated the influence of GST polymorphisms on the development of diseases such as cataract and glaucoma in patients with T2DM in Grande Vitória, Espírito Santo, Brazil. Methods: GSTM1 and GSTT1 polymorphisms were investigated using a multiplex PCR technique. PCR-RFLP was used for the GSTP1 gene. Statistical analysis was performed with Fisher's exact test or the chi-square test, with P-value <0.05. Results: There was no relationship between GSTM1, GSTT1, or GSTP1 polymorphisms and the occurrence of diseases such as glaucoma and cataract in patients with T2DM. Conclusion: Our data suggest that the GSTM1 and GSTT1 null polymorphisms and the ile105Val polymorphism in the GSTP1 gene are not associated with individual susceptibility to the development of ophthalmic complications in persons with T2DM. (AU)

Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis

Abstract Objective: To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a metaanalysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265. Methods: A literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI). Results: The meta-analysis produced overall OR of 1.42 (95% CI 1.36-1.49, P < 0.00001), 1.41 (95% CI 1.36-1.46, P < 0.00001) and 1.34 (95% CI 1.26-1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70-1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86-1.43, P = 0.41) or rs10489265 (OR 1.17,95% CI 0.94-1.47, P = 0.17) polymorphism with SLE susceptibility, respectively. Conclusions: Our meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.

Exploring the potential impact of nutritionally actionable genetic polymorphisms on idiopathic male infertility: a review of current evidence / 亚洲男科学杂志(英文版)

Infertility affects about 15% of the world's population. In 40%-50% of infertile couples, a male factor underlies the problem, but in about 50% of these cases, the etiology of male infertility remains unexplained. Some clinical data show that lifestyle interventions may contribute to male reproductive health. Cessation of unhealthy habits is suggested for preserving male fertility; there is growing evidence that most preexisting comorbidities, such as obesity and metabolic syndrome, are highly likely to have an impact on male fertility. The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility. Although these polymorphisms are not directly connected with male infertility, they may have a role in specific conditions associated with it, that is, metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage. Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility, but their results have not been synthesized. We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation, by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021

BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Association between estrogen, vitamin d and microrna17 gene polymorphisms and periapical lesions

Abstract This study evaluated the association between polymorphisms in genes encoding estrogen receptors 1 (ESR1) and 2 (ESR2), vitamin D receptor (VDR) and in microRNA17 (which binds to ESR1 and VDR) with persistent apical periodontitis (PAP) after the endodontic treatment. We included 162 patients who completed endodontic treatment at least one year ago and presented apical periodontitis at the beginning of the root canal therapy. Clinical and radiographic exams were performed to evaluate the presence of PAP or healthy periradicular tissues (healed). Saliva samples were collected as a genomic DNA. The genotyping of ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938), VDR (rs739837 and rs2228570) and miRNA17 (rs4284505) were performed by real-time PCR. Chi-square test was used to the distribution of genotype and allele frequencies. Haplotype analysis was also performed. Eighty-nine patients were included in the "healed" group and 73 in the "PAP" group. No association was found between the allelic and genotypic polymorphisms studied and PAP (p>0.05). Haplotype analysis also did not demonstrated an association (p>0.05). In conclusion, the genetic polymorphisms in ESR1, ESR2, VDR and miRNA17 are not associated with PAP.

Resumo Este estudo avaliou a associação entre polimorfismos em genes que codificam os receptores de estrogênio 1 (ESR1) e 2 (ESR2), receptor de vitamina D (VDR) e no microRNA17 (que se liga à ESR1 e VDR) e a periodontite apical persistente (PAP) após o tratamento endodôntico. Foram incluídos 162 pacientes com tratamento endodôntico concluído há pelo menos um ano e que apresentavam periodontite apical no início da terapia endodôntica. Exames clínicos e radiográficos foram realizados para avaliar a presença de PAP ou tecidos perirradiculares saudáveis (cicatrizados). As amostras de saliva foram coletadas como fonte de DNA genômico. A genotipagem de ESR1 (rs2234693 e rs9340799), ESR2 (rs1256049 e rs4986938), VDR (rs739837 e rs2228570) e miRNA17 (rs4284505) foram realizadas por PCR em tempo real. O teste do qui-quadrado foi utilizado para a distribuição das frequências genotípicas e alélicas. A análise de haplótipos também foi realizada. Oitenta e nove pacientes foram incluídos no grupo "curado" e 73 no grupo "PAP". Não foi encontrada associação entre os polimorfismos alélicos e genotípicos estudados e a PAP (p>0,05). Concluí-se que os polimorfismos genéticos em ESR1, ESR2, VDR e miRNA17 não estão associados à PAP.

Epidemiological and TNFα polymorphism evaluation in patients with cryptococcal meningitis treated at a referral hospital in North Brazil

Abstract INTRODUCTION: The present study evaluated the epidemiology of cryptococcal meningitis and TNFα gene polymorphisms in patients at a reference hospital in northern Brazil. METHODS: Samples from 25 patients infected with Cryptococcus spp. were collected to confirm the infection and to analyze the TNFα gene polymorphisms. RESULTS: Cryptococcus neoformans was detected as the predominant etiological agent (100%) in HIV-positive patients. No genetic polymorphic changes were found. CONCLUSIONS: No correlation was observed between the analyzed TNFα polymorphisms and cryptococcal meningitis.

Polimorfismos genéticos da Alanina--Glioxilato Aminotransferase 2 (AGXT2) associados à disfunção erétil e marcadores de resposta aos iPDE-5 / Genetic polymorphysms of alanine - Glyoxylate Aminotransferase 2 (AGXT2) associated with erectile dysfunction and response markers to iPDE-5

Disfunção Erétil (DE) é caracterizada pela incapacidade de obter ou manter uma ereção suficiente para que ocorra atividade sexual satisfatória. Uma das principais características da DE está relacionada ao possível déficit na produção de Óxido Nítrico (NO) no corpo humano. O NO é produzido através da L-arginina, via Óxido Nítrico Sintase neuronal, endotelial e induzível (nNOS, eNOS e iNOS). As dimetilargininas assimétrica (ADMA) e a simétrica (SDMA) são formas metiladas da L-arginina e atuam como agentes inibidores das NOS, portanto os níveis aumentados de ADMA e SDMA estão associados a menor produção de NO. Uma das principais enzimas responsáveis pela degradação de ADMA e SDMA é a AGXT2, codificada pelo gene homônimo. Estudos têm relacionado polimorfismos genéticos da AGXT2 a doenças cardiovasculares e todo o contexto do NO, podendo ser utilizados como marcadores para o risco de desenvolvimento de DE. Os objetivos deste estudo visam relacionar polimorfismos genéticos da AGXT2 (rs37369 e rs16899974) ao risco para desenvolvimento de DE e ao resultado da terapia medicamentosa com inibidores da fosfodiesterase 5 (iPDE-5). Trata-se de um estudo de dois braços, sendo o primeiro um estudo caso-controle e outro apenas com os pacientes em uso de iPDE-5, avaliando a resposta a essa classe de fármacos. A função erétil dos voluntários desta pesquisa foi avaliada através da escala Índice Internacional de Função Erétil (IIEF). Os genótipos foram obtidos por PCR em tempo real. Foram encontrados associações significativas entre os marcadores genéticos e a resposta ao sildenafil e aos níveis de nitrito e ADMA. Quanto ao estudo caso-controle não foram encontrados associações significativas para este estudo

Erectile Dysfunction (ED) is characterized by the inability to obtain or maintain an erection sufficient for satisfactory sexual activity to occur. One of the main features of ED is related to the possible deficit in the production of nitric oxide (NO) in the human body. NO is produced through L-arginine via neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS). Asymmetric (ADMA) and symmetrical (SDMA) dimethylarginines are methylated forms of L-arginine and act as NOS inhibitory agents, so increased levels of ADMA and SDMA are associated with decreased NO production. One of the main enzymes responsible for the degradation of ADMA and SDMA is AGXT2, encoded by the homonymous gene. Studies have linked genetic polymorphisms of AGXT2 to cardiovascular diseases and the entire context of NO, and can be used as markers for the risk of developing ED. The objectives of this study were to correlate AGXT2 genetic polymorphisms (rs37369 and rs16899974) with the risk for developing ED and the outcome of the drug therapy with phosphodiesterase 5 inhibitors (iPDE-5). It is a two-arm study, the first being a case-control study and the other only with patients using iPDE-5, evaluating the response to this class of drugs. The erectile function of the volunteers of this research was evaluated through the International Index of Erectile Function (IIEF) scale. Genotypes were obtained by real-time PCR. Significant associations were found between genetic markers and response to sildenafil and levels of nitrite and ADMA. Regarding the case-control study, no significant associations were found for this study

NR3C1 Polymorphisms for Genetic Susceptibility to Schizophrenia

OBJECTIVES: Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia.METHODS: Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models).RESULTS: The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16–2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11–2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13–2.10, p = 0.0067).CONCLUSIONS: This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

Effects of Obesity and Family History of Diabetes on the Association of CETP rs6499861 with HDL-C Level in Korean Populations

OBJECTIVES: The aim of this study was to examine the associations of cholesterol ester transfer protein (CETP) rs6499861 and rs12708980 with high-density lipoprotein cholesterol (HDL-C) considering obesity and family history of diabetes (FHD) in Korean men and women. METHODS: We analyzed the association of CETP single nucleotide polymorphisms (SNPs) with HDL-C among individuals selected from a hospital (n=4 294) and the Bundang-gu area in Korea (n=2 304). RESULTS: We found that the CETP SNP rs6499861 was associated with a lower HDL-C level (effect per allele: −2.044 mg/dL, p<0.0001). Individuals with a rs6499861 CG/GG genotype had a 1.45-fold higher risk of an abnormal level of HDL-C (<40 mg/dL) than those with a CC genotype. This genotype-HDL-C association was stronger in women (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.39–2.85) compared with men (OR, 1.33; 95% CI, 1.10–1.61) and in women with a FHD (OR, 4.82; 95% CI, 1.86–12.5; p=0.0012) compared with women without a family history. Relative to individuals with a CC genotype and body mass index (BMI) <25.69 kg/m², individuals with a CG/GG genotype and BMI ≥25.69 kg/m² had an OR (95% CI) of 2.61 (1.97–3.47). CONCLUSIONS: These findings indicate that CETP variants are linked to HDL-C level in Koreans and that this link is stronger in obese men and in women who have a FHD.