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Article in Chinese | WPRIM | ID: wpr-879524


OBJECTIVE@#To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing.@*RESULTS@#The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth.@*CONCLUSION@#Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.

Child, Preschool , China , Congenital Abnormalities/genetics , Female , Genetic Association Studies , Genetic Testing , Humans , Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics , Phenotype , Pregnancy , Syndrome , Whole Exome Sequencing
Braz. arch. biol. technol ; 64: e21200133, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249209


Abstract Abscisic acid (ABA) is a plant hormone that plays several roles in plant development. The de novo synthesis and the reversible inactivation of ABA have been largely described in the literature; however, the degradation of ABA, promoted by the enzymes Abscisic Acid 8'-Hydroxylase, encoded by the CYP707A gene family, is still poorly elucidated. Strawberry (Fragaria x ananassa) has been used as a model to study the ABA-dependent maturation process of non-climacteric fruits, and the ABA-dependent response to abiotic stress. However, the CYP707A genes from this species have not been fully described and characterized. In this perspective, FaCYP707A sequences were identified from strawberry fruit transcriptome and several structural and comparative genomic analyzes were performed. Moreover, the expression of the FaCYP707A sequences identified was investigated in fruits under salt stress and ABA application. Four putative FaCYP707A were identified and the structural analysis confirmed the identity of three of them. The phylogenetic analysis allowed to determine their homologous in other plant species and to predict their evolutionary history; and the expression profile of the FaCYP707As demonstrated that FaCYP707A3 seems to be involved in the response against salt stress in an ABA-dependent manner. Moreover, the interaction network analysis pointed out proteins involved in the ABA metabolism, heavy metal homeostasis and detoxification, and cell wall dissemble. This study characterized for the first time the CYP707A gene family in F. ananassa; this information will guide future studies in order to develop biofortified fruits and stress tolerant plants.

Phylogeny , Stress, Physiological , Abscisic Acid , Genetic Association Studies
Article in Chinese | WPRIM | ID: wpr-826531


OBJECTIVE@#To explore the genotype-phenotype correlation of Cardio-facio-cutaneous syndrome (CFCS) caused by MAP2K1 gene variants.@*METHODS@#Genomic DNA was extracted from peripheral blood sample from a child patient and his parents. Whole exome sequencing (WES) was carried out for the patient. Suspected variant was verified by Sanger sequencing.@*RESULTS@#The patient was a 1-year-8-month old Chinese male who manifested short stature, psychomotor retardation, relative macrocephaly, distinctive facial features, and congenital heart disease. WES test revealed a heterozygous missense c.389A>G (p.Tyr130Cys) variant in the MAP2K1 gene. Sanger sequencing has confirmed the variant as de novo. According to ACMG/AMP guidelines, the variant was classified as pathogenic.@*CONCLUSION@#Compared with previously reported CFCS cases due to MAP2K1 variants. The patient showed obvious behavioral problems, good appetite and tricuspid regurgitation, which may to be novel features for CFCS.

China , Ectodermal Dysplasia , Genetics , Facies , Failure to Thrive , Genetics , Genetic Association Studies , Genetic Variation , Heart Defects, Congenital , Genetics , Heterozygote , Humans , Infant , MAP Kinase Kinase 1 , Genetics , Male , Mutation , Whole Exome Sequencing
Article in Chinese | WPRIM | ID: wpr-826529


Bartter syndrome is an inherited metabolic disorder characterized by hypokalemic alkalosis and high rennin-angiotensin-aldosteronism which can occur at all ages but mainly in childhood. Classical Bartter syndrome is caused by loss-of-function variants in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB), which is a common type of Bartter syndrome characterized with diverse clinical manifestations ranging from severe to very mild. This article reviews the function and mechanism of CLCNKB variants in Chinese population and the genotype-phenotype correlation of CLCNKB variants in classical Bartter syndrome.

Asian Continental Ancestry Group , Bartter Syndrome , Genetics , Pathology , Chloride Channels , Genetics , Genetic Association Studies , Humans , Research
J. appl. oral sci ; 28: e20190583, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1090773


Abstract Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and −149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism −149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

Humans , Male , Female , Adult , Middle Aged , Aged , Periodontitis/genetics , Polymorphism, Genetic , DNA Methylation/genetics , MicroRNAs/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Polymorphism, Restriction Fragment Length , Catalase/genetics , Case-Control Studies , Polymerase Chain Reaction , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Genetic Association Studies , Superoxide Dismutase-1/genetics , Genotype
An. bras. dermatol ; 94(6): 658-663, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054887


Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.

Humans , Male , Female , Adult , Middle Aged , Psoriasis/genetics , Interleukins/genetics , Mutation , Phenotype , Psoriasis/pathology , China , Sequence Analysis, DNA , Statistics, Nonparametric , Asian Continental Ancestry Group/genetics , Amplified Fragment Length Polymorphism Analysis , Genetic Association Studies , Foot Dermatoses/genetics , Foot Dermatoses/pathology , Hand Dermatoses/genetics , Hand Dermatoses/pathology , Heterozygote
Arq. bras. oftalmol ; 82(6): 501-506, Nov.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1038690


ABSTRACT Purpose: To investigate the potential associations between keratoconus and catalase rs1001179, superoxide dismutase 2 rs4880, and glutathione peroxidase 1 rs1050450 gene polymorphisms in a Turkish population. Methods: The study group included 121 unrelated keratoconus patients and 94 unrelated healthy controls. Blood samples (200 ml) were collected from all patients and controls to isolate genomic DNA. Genotyping was performed to identify rs1001179, rs4880, and rs1050450 using real-time polymerase chain reaction (PCR). Genotype and allele frequencies were calculated; their associations with keratoconus risk were assayed, and the association with keratoconus risk and demographic factors was examined. Results: Glutathione peroxidase 1 rs1050450 polymorphism was present in 41% cases compared with 29% controls (OR=1.66; 95% CI=1.11-2.50; p=0.014). No association was observed between catalase rs1001179 and SOD2 rs4880 polymorphisms and keratoconus (for all, p>0.05). Conclusions: This study evaluated possible relationships between rs1050450, rs1001179, and rs4880 polymorphisms and keratoconus susceptibility. We found a possible association between glutathione peroxidase 1 rs1050450 polymorphism and an increased risk of keratoconus. However, the genotype and allele frequencies were identical in the catalase rs1001179 and superoxide dismutase 2 rs4880 polymorphisms. Further studies are needed to analyze the effect of such variations in identifying keratoconus susceptibility.

RESUMO Objetivo: Investigar as possíveis associações entre o ceratocone e os polimorfismos rs1001179 da catalase, rs4880 da superóxido-dismutase 2 e rs1050450 da glutationa-peroxidase 1 rs1050450 em uma população turca. Métodos: O grupo de estudo incluiu 121 pacientes com ceratocone não relacionados e 94 controles saudáveis também sem pa rentesco. Amostra de sangue (200 mL) foram coletadas de todos os pacientes e controle para isolar o DNA genômico. A genotipagem foi realizada para identificar rs1001179, rs4880 e rs1050450 utilizando a reação em cadeia da polimerase (PCR) em tempo real. As frequências de genótipos e alelos foram calculadas, suas associações com o risco de ceratocone foram avaliadas, e a associação com risco de ceratocone e fatores demográficos foi examinada. Resultados: O polimorfismo da glutationa-peroxidase 1 rs1050450 estava presente em 41% dos casos, comparado com 29% dos controles (OR=1,66, IC 95%=1,11-2,50; p=0,014). Não foi observada associação entre o ceratocone e os polimorfismos rs1001179 e SOD2 rs4880 da catalase (para todos, p>0,05). Conclusões: Este estudo avaliou possíveis relações entre os polimorfismos rs1001179, rs4880 e suscetibilidade a cerato cone. Encontramos uma possível associação entre po limorfis mo da glutationa-peroxidase 1 rs1050450 e um risco aumentado de ceratocone. No entanto, o genótipo e as frequências alélicas foram idênticas nos polimorfismos rs1001179 da catalase e superóxido-dismutase 2 rs4880. Mais estudos são necessários para esclarecer o efeito dessas va riações na detecção da sus cetibilidade ao ceratocone.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Polymorphism, Single Nucleotide/genetics , Glutathione Peroxidase/genetics , Keratoconus/genetics , Reference Values , Superoxide Dismutase/genetics , Turkey , Catalase/genetics , Case-Control Studies , Polymerase Chain Reaction , Risk Factors , Genetic Association Studies , Genotyping Techniques , Gene Frequency
Int. braz. j. urol ; 45(5): 901-909, Sept.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040082


ABSTRACT Purpose It has been reported that calcitonin receptor (CALCR) gene polymorphisms might be associated with calcium stone urolithiasis. Owing to mixed and inconclusive results, we conducted a meta-analysis to summarize and clarify this association. Materials and Methods A systematic search of studies on the association between CALCR gene polymorphisms and calcium stone urolithiasis susceptibility was conducted in databases. Results Odds ratios and 95% confidence intervals were used to pool the effect size. Five articles were included in our meta-analysis. Conclusions CALCR rs1801197 might be associated with increased risk of calcium stone urolithiasis. There is insufficient data to fully confirm the association between CALCR rs1042138 and calcium stone urolithiasis susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.

Humans , Male , Female , Receptors, Calcitonin/genetics , Polymorphism, Single Nucleotide , Urolithiasis/genetics , Calcium/metabolism , Risk Factors , Risk Assessment , Genetic Association Studies
An. bras. dermatol ; 94(4): 429-433, July-Aug. 2019. tab
Article in English | LILACS | ID: biblio-1038308


Abstract: Background: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. Objective: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. Methods: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. Results: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. Study limitations: Lack of studies on various racial or ethnic groups and small sample size. Conclusion: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.

Humans , Male , Female , Adult , Behcet Syndrome/genetics , Polymorphism, Single Nucleotide , Hepatitis A Virus Cellular Receptor 2/genetics , Case-Control Studies , Logistic Models , Risk Factors , Risk Assessment , Alleles , Genetic Association Studies , Multiplex Polymerase Chain Reaction , Gene Frequency , Iran
Rev. méd. Chile ; 147(8): 965-976, ago. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058631


Background: Type 2 diabetes etiology has a strong genetic component. More than 20 genetic variants have been associated with diabetes and other metabolic markers. However, the polymorphism rs7903146 of the TCF7L2 gene has shown the strongest association. Aim: To investigate the association of TCF7L2 (rs7903146) genotype with adiposity and metabolic markers in the Chilean adult population. Material and Methods: The association of TCF7L2 (rs7093146) with adiposity and metabolic markers was studied in 301 participants. The outcomes of the study were adiposity markers (body weight, body mass index (BMI), fat mass and waist circumference) and metabolic markers (blood glucose, insulin, HOMA-IR, lipid profile, high sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) and leptin). Results: There was an association between the polymorphism TCF7L2 genotype and fasting blood glucose. The latter increased by 4.86 mg/dl per each copy of the risk allele [(95% confidence intervals (CI): 0.48; 9.24), p = 0.03] in the unadjusted adjusted model. However, this association was slightly attenuated in the fully adjusted model [4.38 mg/dl (95% IC: 0.16; 8.60), p = 0.04)]. There were no associations between the TCF7L2 genotype and any other metabolic or adiposity outcome. Conclusions: These findings confirm the association between the TCF7L2 (rs7903146) and fasting glucose in the Chilean population. However, further studies are needed to confirm the association between the TCF7L2 and diabetes risk in the Chilean population.

Humans , Male , Female , Adult , Middle Aged , Young Adult , Polymorphism, Single Nucleotide , Diabetes Mellitus, Type 2/genetics , Adiposity/genetics , Transcription Factor 7-Like 2 Protein/genetics , Reference Values , Blood Glucose/genetics , Genetic Markers , Linear Models , Chile , Anthropometry , Nutritional Status , Cross-Sectional Studies , Risk Factors , Diabetes Mellitus, Type 2/metabolism , Alleles , Adiposity/ethnology , Genetic Association Studies , Gene Frequency , Genotype
Rev. ADM ; 76(3): 156-161, mayo-jun. 2019. ilus, tab
Article in Spanish | LILACS | ID: biblio-1022128


Durante el crecimiento y desarrollo de la cabeza, ésta lo hace en diferentes direcciones y proporciones, habiendo un límite entre la armonía /desarmonía conocido como umbral. Se hace referencia a este concepto, la forma de escribirlo y leerlo por medio de un código que lo simboliza. Objetivo: Poner al alcance de la comunidad médica un código de lectura e identificación de fenotipos craneofaciales sindrómicos y no sindrómicos. Conclusiones: Se considera que este concepto de umbral craneofacial y su código de lectura pueden ser usados en la enseñanza e investigación de la armonía-desarmonía durante el crecimiento y desarrollo de la cabeza, resultando ser de gran utilidad en la comprensión rápida y sencilla de la lectura del fenotipo craneofacial (AU)

During the growth and development of the head, it does so in different directions and proportions, there being a limit between the harmony / disharmony known as threshold. Reference is made to this concept, the way of writing it and reading it by means of a code that symbolizes it. Objective: To put within reach of the medical community, a code of reading and identification of syndromic and non-syndromic craniofacial phenotypes. Conclusions: It is considered that this concept of a craniofacial threshold and its reading code can be used in the teaching and research of harmony / disharmony during the growth and development of the head, being very useful in the quick and easy comprehension of the reading of the craniofacial phenotype (AU)

Humans , Phenotype , Multifactorial Inheritance , Maxillofacial Development , Prognathism , Retrognathia , Cephalometry , Craniofacial Abnormalities/classification , Codes , Genetic Association Studies , Head/growth & development , Malocclusion/classification
Rev. Assoc. Med. Bras. (1992) ; 65(6): 786-790, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1012975


SUMMARY OBJECTIVE: This study was to assess the genetic association of copy number variations in two genes (PRKAB2 and PPM1K) located in two regions (tetralogy of Fallot and ventricular septal defect) in a Chinese Han population. METHODS: A total of 200 congenital heart disease patients (100 tetralogy of Fallot patients and 100 ventricular septal defect patients) and 100 congenital heart defect-free controls were recruited, and quantitative real-time PCR analysis was used to replicate the association of two copy number variations with congenital heart defects in a Chinese Han population. RESULTS: One deletion at PRKAB2 and one duplication at PPM1K were found in two of the tetralogy of Fallot patients, respectively; while all these regions were duplicated in both ventricular septal defect patients and in the 100 congenital heart defects-free controls. CONCLUSIONS: We replicated the copy number variations at the disease-candidate genes of PRKAB2 and PPM1K with tetralogy of Fallot in a Chinese Han population, and in patients with ventricular septal defect mutations in these two genes were not found. These results indicate the same molecular population genetics exist in these two genes with different ethnicity. This shows that these two genes are possibly specific pf tetralogy of Fallot candidates.

RESUMO OBJETIVO: Este estudo teve como objetivo avaliar a associação genética do número de cópias em dois genes (PRKAB2 e PPM1K) localizados em duas regiões (tetralogia de Fallot e comunicação interventricular) em uma população chinesa da etnia Han. METODOLOGIA: Um total de 200 pacientes com doença cardíaca congênita (100 pacientes com tetralogia de Fallot e 100 com comunicação interventricular) e 100 indivíduos livres de defeitos cardíacos congênitos foram recrutados, e uma análise quantitativa de PCR em tempo real foi utilizada para replicar a associação de duas variações de número de cópia de defeitos cardíacos congênitos, em uma população chinesa da etnia Han. RESULTADOS: Uma supressão em PRKAB2 e duplicação em PPM1K foram encontradas em dois pacientes com tetralogia de Fallot, respectivamente; todas essas regiões estavam duplicadas nos pacientes com comunicação interventricular e nos 100 indivíduos livres de defeitos cardíacos congênitos. CONCLUSÃO: Nós replicado a variações no número de cópias de genes candidatos de doença PRKAB2 e PPM1K com tetralogia de Fallot em uma população chinesa da etnia Han; em pacientes com comunicação interventricular, não foram encontradas mutações nesses dois genes. Estes resultados indicam que a mesma genética de população molecular existe nestes dois genes em diferentes etnias. Isso mostra que esses dois genes são possivelmente candidatos a genes específicos de tetralogia de Fallot.

Humans , Tetralogy of Fallot/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , AMP-Activated Protein Kinases/genetics , DNA Copy Number Variations , Heart Septal Defects, Ventricular/genetics , Reference Values , Case-Control Studies , Genetic Association Studies , Real-Time Polymerase Chain Reaction
Rev. Assoc. Med. Bras. (1992) ; 65(6): 923-929, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1012981


SUMMARY OBJECTIVE: To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. METHODS: We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. RESULTS: A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. CONCLUSION: The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.

RESUMO OBJETIVO: Investigar a associação entre o polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e a susceptibilidade da etnia Han chinesa para a doença arterial coronariana (DAC). Métodos: Foi realizada uma pesquisa abrangente para o valor de OR (Odds Ratio) de contraste entre o grupo de polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e o grupo de doença arterial coronariana (DAC) como um índice de eficácia. Uma meta-análise (Stata 12,0) foi utilizada para testar a heterogeneidade dos resultados, combinar os valores de eficácia, realizar análises de sensibilidade e de avaliação básica. RESULTADOS: Um total de 638 estudos foram encontrados sobre a associação entre polimorfismos do gene da enzima conversora da angiotensina e doença arterial coronariana, dos quais 44 satisfaziam os critérios de inclusão. Nosso estudo incluiu 6246 casos e 5713 controles. O teste de heterogeneidade de cada estudo (p < 0,001) foi realizado seguindo o modelo de efeito randômico. O valor de OR para DD/ID+II foi 1,95, com 95% de intervalo de confiança de (95%CI) (1,66-2,29). O valor de OR para II/DI+DD foi 0,63, com 95% IC (0,55-0,72). A figura do funil é basicamente simétrica e os resultados da análise de sensibilidade foram estáveis. CONCLUSÃO: O genótipo DD do gene da enzima conversora da angiotensina podem ser um fator de risco mais fraco para doença coronariana na população chinesa Han.

Humans , Polymorphism, Genetic , Coronary Artery Disease/genetics , Peptidyl-Dipeptidase A/genetics , Genetic Association Studies , Coronary Artery Disease/etiology , China/ethnology , Risk Factors
Arq. neuropsiquiatr ; 77(3): 166-173, Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001345


ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

RESUMO Atualmente não se sabe como os fatores genéticos podem influenciar o curso clínico da esclerose múltipla (EM). Objetivo: Examinamos o impacto dos polimorfismos CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) no risco de progressão da incapacidade, gravidade e resposta aos tratamentos imunomoduladores de primeira linha. Métodos: O DNA genômico foi extraído de amostras de sangue. Utilizamos o software ABI3730xl e GeneMapper v.4.0 (Applied Biosystems) para identificar variações genotípicas. Todos os pacientes foram acompanhados e reavaliados clinicamente em intervalos de três meses. A progressão da incapacidade foi medida pela EDSS e a gravidade da doença pelo MSSS. Resultados: Incluímos 37 homens e 80 mulheres. Não encontramos evidências sobre a influência dos SNPs estudados no EDSS e na resposta terapêutica aos fármacos avaliados. Realizamos uma análise de regressão logística com o MSSS e observamos uma evolução menos grave da EM associada aos tipos selvagens CIITA −168AA e CIITA +1614GG, pois a chance do paciente atingir MSSS2 e MSSS3 diminuiu em 61%/75%, e 66/75% respectivamente (p < 0,0001). Embora menos significativo, o CIITA +1614GC também foi relacionado com evolução menos grave da EM e a chance do paciente atingir o MSSS3 diminuiu 79% (p = 0,015). Nós também observamos que o genótipo CIITA −168GG foi mais frequente no MSSS2 e MSSS3 e teve uma razão de chance 40% menor para atingir forma mais grave da EM. Conclusão: Estes dados sugerem que os polimorfismos CIITA −168AA, CIITA +1614GG e CIITA +1614GC podem estar associados a um melhor curso clínico da EM. Este conhecimento pode ser útil para uma melhor compreensão da EM e o seu manejo terapêutico.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Nuclear Proteins/genetics , Trans-Activators/genetics , Disease Progression , Polymorphism, Single Nucleotide/genetics , Multiple Sclerosis/genetics , Time Factors , Severity of Illness Index , Logistic Models , Retrospective Studies , Interferon-beta/therapeutic use , Disability Evaluation , Kaplan-Meier Estimate , Genetic Association Studies , Glatiramer Acetate/therapeutic use , Gene Frequency , Genotype , Immunologic Factors/therapeutic use , Multiple Sclerosis/mortality , Multiple Sclerosis/drug therapy
Arq. neuropsiquiatr ; 77(2): 73-79, Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-983882


ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

RESUMO Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro.

Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Parkinson Disease/genetics , Glucosylceramidase/genetics , Mutation/genetics , Polymorphism, Restriction Fragment Length , Brazil , Case-Control Studies , Polymerase Chain Reaction , Cross-Sectional Studies , Risk Factors , Age of Onset , Genetic Association Studies
Article in English | WPRIM | ID: wpr-762588


Deletion on the short arm of chromosome 18 is a rare disorder characterized by intellectual disability, growth retardation, and craniofacial malformations (such as prominent ears, microcephaly, ptosis, and a round face). The phenotypic spectrum is wide, encompassing a range of abnormalities from minor congenital malformations to holoprosencephaly. We present a case of a 2-year-old girl with ptosis, a round face, broad neck with low posterior hairline, short stature, and panhypopituitarism. She underwent ventilation tube insertion for recurrent otitis media with effusion. Brain magnetic resonance imaging showed an ectopic posterior pituitary gland and a shallow, small sella turcica with poor visualization of the pituitary stalk. Cytogenetic and chromosomal microarray analysis revealed a de novo deletion on the short arm of chromosome 18 (arr 18p11.32p11.21[136,227–15,099,116]x1). She has been treated with recombinant human growth hormone (GH) therapy since the age of 6 months after diagnosis of GH deficiency. Her growth rate has improved without any side effects from the GH treatment. This case expands the phenotypic spectrum of 18p deletion syndrome and emphasizes the positive impact of GH therapy on linear growth in this syndrome characterized by growth deficiency. Further studies are required to define the genotype-phenotype correlation according to size and loci of the deletion in 18p deletion syndrome and to predict prognosis.

Arm , Brain , Child, Preschool , Chromosomes, Human, Pair 18 , Cytogenetics , Diagnosis , Ear , Female , Genetic Association Studies , Growth Hormone , Holoprosencephaly , Human Growth Hormone , Humans , Intellectual Disability , Magnetic Resonance Imaging , Microarray Analysis , Microcephaly , Neck , Otitis Media with Effusion , Pituitary Gland , Pituitary Gland, Posterior , Prognosis , Sella Turcica , Ventilation
Article in Chinese | WPRIM | ID: wpr-771977


With the advance of high-throughout sequencing technology and its extensive application in clinical diagnosis, analysis of sequencing data has become an important part of clinical diagnosis. To date, the development and establishment of various software and databases have made it convenient to extract useful information from massive amounts of high-throughput sequencing data. However, it is still a challenge for correlating the clinical-genetic diagnosis based on the above-mentioned sequence data with the screened DNA variations and disease phenotypes. Further validation of the proposed pathogenesis with the discovered molecular defects are required. Here a comprehensive review is provided for the strategies of sequencing data analysis, commonly used phenotype-genotype correlation tools, and functional analysis and verification methods for the genetic diagnosis.

Genetic Association Studies , High-Throughput Nucleotide Sequencing , Humans , Phenotype , Sequence Analysis, DNA , Software
Article in English | WPRIM | ID: wpr-719693


For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Recently, a combinatorial analysis of single nucleotide polymorphisms (SNPs) identified by GWAS has been used to develop sets of genetic markers able to more accurately stratify asthma subtypes. In this review, we discuss the implications of the identified SNPs in diagnosis of asthma and its subtypes and the progress being made in combinatorial analysis of genetic variants.

Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Asthma , Asthma, Occupational , Biomarkers , Diagnosis , Genetic Association Studies , Genetic Markers , Genetic Techniques , Genome-Wide Association Study , Hope , Pathology , Phenotype , Polymorphism, Single Nucleotide
Laboratory Animal Research ; : 165-171, 2019.
Article in English | WPRIM | ID: wpr-786407


Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.

Animals , Computational Biology , Genes, vif , Genetic Association Studies , Humans , Mice , Phenotype , Systems Biology
Article in English | WPRIM | ID: wpr-785582


BACKGROUND: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR , and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH.METHODS: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records.RESULTS: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months-3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3).CONCLUSION: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

Age of Onset , Dialysis , Genetic Association Studies , Genotype , Humans , Hydrogen-Ion Concentration , Hyperoxaluria, Primary , Kidney Failure, Chronic , Kidney Transplantation , Liver , Liver Transplantation , Medical Records , Organ Transplantation , Phenotype , Retinaldehyde , Retrospective Studies , Transplants