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Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 128-133, sept. 2023. tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1517860


Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Humans , Female , Breast Neoplasms/genetics , Menopause, Premature , BRCA1 Protein/genetics , Hormone Replacement Therapy , BRCA2 Protein/genetics , Salpingo-oophorectomy/statistics & numerical data , Progesterone/adverse effects , Progesterone/therapeutic use , Breast Neoplasms/prevention & control , Cardiovascular Diseases/epidemiology , Risk Factors , Genetic Predisposition to Disease , Estrogens/adverse effects , Estrogens/therapeutic use
Article in Chinese | WPRIM | ID: wpr-986984


OBJECTIVE@#To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS.@*METHODS@#This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions.@*RESULTS@#Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0).@*CONCLUSION@#The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.

Humans , Case-Control Studies , Genetic Predisposition to Disease , Interleukin-10/genetics , Polymorphism, Single Nucleotide , Spondylitis, Ankylosing/genetics , Transcriptional Elongation Factors/genetics , Nuclear Proteins/genetics
Chinese Journal of Hepatology ; (12): 653-658, 2023.
Article in Chinese | WPRIM | ID: wpr-986187


Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

Humans , Genetic Predisposition to Disease , Prospective Studies , Risk Factors , Chemical and Drug Induced Liver Injury/genetics , Drug-Related Side Effects and Adverse Reactions , Liver
Chinese Medical Journal ; (24): 1671-1679, 2023.
Article in English | WPRIM | ID: wpr-980972


BACKGROUND@#A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities.@*METHODS@#We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer.@*RESULTS@#During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk.@*CONCLUSION@#These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.

Humans , Prospective Studies , Stomach Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Risk Factors , Multifactorial Inheritance/genetics , Polymorphism, Single Nucleotide/genetics , Genome-Wide Association Study
Article in English | WPRIM | ID: wpr-971082


The "Lübeck disaster", twins studies, adoptees studies, and other epidemiological observational studies have shown that host genetic factors play a significant role in determining the host susceptibility to Mycobacterium tuberculosis infection and pathogenesis of tuberculosis. From linkage analyses to genome-wide association studies, it has been discovered that human leucocyte antigen (HLA) genes as well as non-HLA genes (such as SLC11A1, VDR, ASAP1 as well as genes encoding cytokines and pattern recognition receptors) are associated with tuberculosis susceptibility. To provide ideas for subsequent studies about risk prediction of MTB infection and the diagnosis and treatment of tuberculosis, we review the research progress on tuberculosis susceptibility related genes in recent years, focusing on the correlation of HLA genes and non-HLA genes with the pathogenesis of tuberculosis. We also report the results of an enrichment analysis of the genes mentioned in the article. Most of these genes appear to be involved in the regulation of immune system and inflammation, and are also closely related to autoimmune diseases.

Humans , Genome-Wide Association Study , Tuberculosis/genetics , Gene Expression Regulation , Cytokines/genetics , Autoimmune Diseases , Mycobacterium tuberculosis/genetics , Genetic Predisposition to Disease
Article in Chinese | WPRIM | ID: wpr-971081


Biogenetics plays an important role in the pathogenesis of depressive disorder in adolescents. Various genetic polymorphism studies have updated the understanding of adolescent depressive disorder. However, due to the influence of gene-environment interaction and age of puberty, the influence of gene polymorphisms on adolescent depressive disorder is complicated to clarify. Investigating and clarifying the relationship between gene polymorphisms and adolescent depressive disorder will promote the research on the pathogenesis of this disorder and provide a reference for the prevention and treatment of this disorder. This article reviews the genetic polymorphisms related to adolescent depressive disorder.

Humans , Adolescent , Depressive Disorder, Major/genetics , Polymorphism, Genetic , Gene-Environment Interaction , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease
Article in Chinese | WPRIM | ID: wpr-970890


OBJECTIVE@#To assess the association of rs55829688 and rs75315904 polymorphisms of the lncRNA-GAS5 gene with susceptibility to systemic lupus erythematosus (SLE) in Guangxi population.@*METHODS@#Peripheral venous blood samples were collected from the SLE group and control group. Following extraction of genomic DNA, SNPscan and Sanger sequencing were carried out to determine the genotypes for the rs55829688 and rs75315904 loci of the lncRNA-GAS5 gene.@*RESULTS@#No difference was found between the two groups with regard to the genotypic frequencies for rs55829688 and rs75315904 (P > 0.05). However, the frequencies of C allele of rs55829688 between the two groups was significantly different (P < 0.05). In the SLE group, the frequencies of C allele and CT+CC genotype for rs55829688 among SLE patients with nephritis were significantly lower than those of SLE patients without nephritis (P < 0.05). In addition, haplotype analysis showed that the frequency of rs55829688 C/rs75315904 A allele in the SLE group was lower than that of the control group (P < 0.05).@*CONCLUSION@#In Guangxi population, the carrier status of rs55829688 C allele of the lncRNA-GAS5 gene may reduce the risk of SLE and its complicated nephritis, and the rs55829688 C/rs75315904 A haplotype may reduce the risk for SLE.

Humans , Case-Control Studies , China/epidemiology , Gene Frequency , Genetic Predisposition to Disease , Genotype , Lupus Erythematosus, Systemic/genetics , Nephritis , Polymorphism, Single Nucleotide , RNA, Long Noncoding/genetics
Article in Chinese | WPRIM | ID: wpr-970709


Objective: To summarize and analyse of literature on the susceptibility genes of noise induced hearing loss (NIHL) , and the key genes were screened and obtained by bioinformatics method, so as to provide reference for the prevention research of NIHL. Methods: In September 2021, Based on CNKI, NCBI Pubmed database and Web of Science database, this paper conducted bibliometric analysis and bioinformatics analysis on the genetic literature related to the susceptibility to noise-induced hearing loss from 1999 to 2020. Endnote X9 software and the WPS office software were used for bibliometric analysis, and online software STRING and Cytoscape software were used for bioinformatics analysis. Results: A total of 131 literatures were included in the study, involving 40 genes in total. Bibliometric analysis shows that 131 papers which included 36 Chinese articles and 95 English articles were published in 63 biomedical journals; the highest number of published articles was 19 in 2020. Bioinformatics analysis suggests that GAPDH、SOD2、SOD1、CAT、CASP3、IL6 and other genes play a key role in the interaction network. The involved pathways mainly include MAP2K and MAPK activations, PTEN regulation, P53-depardent G1 DNA damage response, signaoling by BRAF and RAF fusions and soon. Conclusion: The study of noise induced hearing loss involves multi gene biological information, and bioinformatics analysis is helpful to predict the occurrence and development of noise induced hearing loss.

Humans , Hearing Loss, Noise-Induced/epidemiology , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Computational Biology , Bibliometrics , Noise, Occupational
Chinese Journal of Epidemiology ; (12): 504-510, 2023.
Article in Chinese | WPRIM | ID: wpr-969935


Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

Humans , Cleft Palate/genetics , Cleft Lip/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease , Risk Factors , Polymorphism, Single Nucleotide
Braz. j. biol ; 83: e244123, 2023. tab
Article in English | LILACS, VETINDEX | ID: biblio-1278562


Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Humans , Toll-Like Receptor 9/genetics , Lupus Erythematosus, Systemic/genetics , Brazil , Pilot Projects , Genetic Predisposition to Disease/genetics , Gene Frequency/genetics
Asian Journal of Andrology ; (6): 404-409, 2023.
Article in English | WPRIM | ID: wpr-981951


Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.

Humans , Male , Fluorides/adverse effects , Semen , Polymorphism, Genetic , Glutathione Transferase/genetics , Glutathione S-Transferase pi/genetics , Infertility, Male/genetics , Genotype , Biomarkers , Genetic Predisposition to Disease , Case-Control Studies
Chinese Journal of Epidemiology ; (12): 1146-1150, 2023.
Article in Chinese | WPRIM | ID: wpr-985646


Mosaic chromosomal alteration (mCA) is referred to as large-scale somatic mutations on chromosomes, which results in diverse karyotypes in body. The mCA is regarded as one of the phenotypes of aging. Studies have revealed its associations with many chronic diseases such as hematopoietic cancers and cardiovascular diseases, but its genetic basis (e.g. genetic susceptibility variants) is still under-investigated. This paper reviews GWAS studies for mCA on autosomal chromosomes and sex chromosomes [mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX)] based on large population, respectively. Most of the genetic susceptibility loci found in studies for autosomal mCA were associated with copy-neutral loss of heterozygosity. The study of sex chromosome mCA focused on mosaic loss mutations. The number of genetic susceptibility loci for mLOY was high (up to 156), but it was relatively less for mLOX.

Humans , Male , Genome-Wide Association Study/methods , Mosaicism , Genetic Predisposition to Disease , Chromosomes, Human, Y , Mutation
Article in Chinese | WPRIM | ID: wpr-985488


Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.

Humans , Adult , Middle Aged , Carcinoma, Hepatocellular/genetics , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Hepatitis B virus/genetics , Liver Neoplasms/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Programmed Cell Death 1 Receptor/genetics
Cad. saúde colet., (Rio J.) ; 31(1): e31010250, 2023. tab, graf
Article in English | LILACS | ID: biblio-1430143


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.

Humans , Male , Female , Tobacco Use Disorder , Genetic Variation , Behavior , Genetic Predisposition to Disease , Nicotine , Polymorphism, Genetic , Receptors, Dopamine , Receptors, Nicotinic , Gender Identity
Gac. méd. espirit ; 24(1): [18], abr. 2022.
Article in Spanish | LILACS | ID: biblio-1404889


RESUMEN Fundamento: La variabilidad clínica de la infección por el SARS-CoV-2 se debe, en parte, a factores genéticos. Objetivo: Describir los principales genes de susceptibilidad a la Covid-19. Metodología: Se realizó una revisión bibliográfica en Google Académico, SciELO, Annual Reviews y PubMed Central. Los descriptores que se utilizaron para la búsqueda de los documentos fueron consultados en el DeCS, estos fueron: SARS-CoV-2, Covid-19, genética y predisposición genética a la enfermedad. Se seleccionaron artículos disponibles a texto completo en inglés y en español, preferentemente de revistas arbitradas por pares. Resultados: Entre los genes implicados en la infección por el SARS-CoV-2 se encuentran DDX1 que promueve la replicación viral, IFITM1, IFITM2, IFITM3, IFNAR2 que codifican proteínas inducidas por el interferón, los genes de receptores (ACE2, ANPEP, DPP4), los genes de proteasas (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) que contribuyen a la entrada viral, genes de la respuesta inmune como ABO y metalopeptidasas como la familia ADAM. Se han detectado polimorfismos genéticos de riesgo. Conclusiones: En la infección por el SARS-CoV-2 se produce una compleja interrelación entre factores ambientales y genéticos que determinan la susceptibilidad de las personas a la Covid y su gravedad. El papel de los genes en la susceptibilidad a la Covid-19 deberá continuar investigándose.

ABSTRACT Background: The clinical variability of SARS-CoV-2 infection is partially due to genetic factors. Objective: To describe the main Covid-19 susceptibility genes. Methodology: A literature review was performed in Google Scholar, SciELO, Annual Reviews and PubMed Central. The descriptors used to search the documents were consulted in DeCS: SARS-CoV-2, Covid-19, genetics and genetic predisposition to disease. Full text articles available in English and Spanish were selected, rather from peer-reviewed journals. Results: Genes involved in SARS-CoV-2 infection include DDX1 which promotes viral replication, IFITM1, IFITM2, IFITM3, IFNAR2 encoding interferon-induced proteins, receptor genes (ACE2, ANPEP, DPP4), protease genes (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) that contribute to viral entry, immune response genes such as ABO and metallopeptidases such as the ADAM family. Risk genetic polymorphisms have been detected. Conclusions: In SARS-CoV-2 infection, there is a complex interaction between environmental and genetic factors that determine the susceptibility of individuals to Covid and its severity. The role of genes in Covid-19 susceptibility should be further investigated.

Coronavirus Infections/genetics , Genetic Predisposition to Disease , Severe acute respiratory syndrome-related coronavirus/genetics
Medisan ; 26(1)feb. 2022. ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1405777


Los sarcomas de partes blandas son tumores malignos que se originan en el tejido conectivo, a partir del mesénquima embrionario. Teniendo en cuenta la existencia de nuevos y constantes cambios en la naturaleza de estos tumores, se realizó una revisión de las publicaciones más recientes para profundizar en las alteraciones genéticas, los síndromes de predisposición y su relación con los sarcomas. Se pudo concluir que aún siguen siendo muy pocos los registros que describen la identificación de dichos síndromes como principal eslabón en el desarrollo de los sarcomas.

The sarcomas of soft parts are malignancies that originate in the connective tissue, starting from the embryonic mesenchyme. Taking into account the existence of new and constant changes in the nature of these tumors, a review of the most recent publications was carried out to deepen in the genetic disorders, the predisposing syndromes and its relationship with sarcomas. It was concluded that the records that describe the identification of these syndromes are still very few as main link in the development of sarcomas.

Sarcoma , Genetic Diseases, Inborn , Sarcoma, Clear Cell , Genetic Predisposition to Disease
Arch. endocrinol. metab. (Online) ; 66(1): 12-18, Jan.-Feb. 2022. tab
Article in English | LILACS | ID: biblio-1364310


ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

Humans , Aldehyde Reductase/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/complications , Diabetic Nephropathies/genetics , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Gene Frequency , Genotype
Rev. Bras. Cancerol. (Online) ; 68(2)Abr.-Jun. 2022.
Article in English | LILACS | ID: biblio-1377810


Introduction: The very aggressive soft tissue and bone pediatric tumor Ewing's sarcoma (ES) is caused in most cases by the chromosomal translocation t(11;22)(q24;q12), which encodes an aberrant chimeric transcription factor (EWS-FLI1) that regulates target genes, including the critical oncogene NR0B1 (Xp21.2),via GGAA-microsatellites. Objective: Analyze the GGAA-microsatellites of NR0B1promoter region of ES patients and healthy subjects in the population investigated. Method: Ten male ES patients and 71 adult healthy males from Rio Grande do Sul state, Brazil, were included in this study. DNA from peripheral blood samples was extracted, amplified by PCR, sequenced by the Sanger method and analyzed by capillary electrophoresis. Total number of GGAA-motifs, length of microsatellite in base pairs, number of segments separated by "A" insertions, and the greatest number of consecutive GGAA-motifs were analyzed as well. Statistical analyses were performed in the SPSS statistical software and p-value <0.05 was considered significant. Results: A total of 21 different alleles was identified in the 81 subjects, with 24.2 allele [(GGAA)7A(GGAA)7A(GGAA)10] being the most frequent, but when comparing the data between the two groups, no significant difference was found. Conclusion: The sample investigated had a wide variation of microsatellite structure, including the presence of rare alleles, allowing the opportunity to describe this population as an essential step to identify genetic implications in ES tumorigenesis

Introdução: O sarcoma de Ewing (ES) é um tumor pediátrico de ossos e partes moles muito agressivo, causado, na maioria das vezes, pela translocação cromossômica t(11;22)(q24;q12), codificando um fator de transcrição quimérico aberrante (EWS-FLI1) que regula genes-alvo, incluindo o oncogene NR0B1 (Xp21.2), via microssatélites GGAA. Objetivo: Analisar os microssatélites GGAA da região promotora de NR0B1 em pacientes com ES e indivíduos saudáveis da população em investigação. Método: Foram incluídos dez pacientes do sexo masculino com diagnóstico de ES e 71 indivíduos adultos hígidos do sexo masculino do Estado do Rio Grande do Sul, Brasil. O DNA foi extraído de sangue periférico e amplificado por PCR, sequenciado pelo método de Sanger e analisado por eletroforese capilar. Foram analisados o número total de repetições GGAA, comprimento total do microssatélite em pares de bases, número de segmentos separados por inserções "A" e maior número de repetições GGAA consecutivas. As análises estatísticas foram realizadas no software estatístico SPSS e o valor de p<0,05 foi considerado significativo. Resultados: Um total de 21 alelos diferentes foi identificado nos 81 indivíduos, com o alelo 24,2 [(GGAA)7A(GGAA)7A(GGAA)10], sendo o mais frequente; mas, ao comparar os dados entre os dois grupos, nenhuma diferença significativa foi encontrada. Conclusão: A amostra estudada é altamente variável em termos de estrutura de microssatélites, incluindo a presença de alelos raros, dando a oportunidade de descrever essa população, o que é uma etapa fundamental na identificação de implicações genéticas na tumorigênese do ES

Introducción: El sarcoma de Ewing (ES) es un tumor pediátrico de huesos y tejidos blandos muy agresivo, que se presenta con mayor frecuencia por translocación cromosómica t(11;22)(q24;q12), que codifica un factor de transcripción quimérico aberrante (EWS-FLI1) que regula los genes diana, incluido el oncogén NR0B1 (Xp21.2), a través de microsatélites GGAA. Objetivo: Analizar los microsatélites GGAA de la región promotora de NR0B1en pacientes con ES y personas sanas de la población investigada. Método: Este estudio incluyó a diez pacientes varones con diagnóstico de ES y 71 varones adultos del estado de Rio Grande do Sul, Brasil. El ADN se extrajo de sangre periférica y se amplificó por PCR, secuenciado por el método de Sanger y analizado por electroforesis capilar. El número total de repeticiones GGAA, longitud total de microsatélites en pares de bases, número de segmentos separados por inserciones "A" y el mayor número de repeticiones GGAA consecutivas fueran analizados. Los análisis estadísticos se realizaron con el software estadístico SPSS y se consideró significativo un valor de p<0,05. Resultados: Se identificaron un total de 21 alelos diferentes en los 81, siendo el alelo 24,2 [(GGAA)7A(GGAA)7A(GGAA)10] el más frecuente, pero al comparar los datos entre los dos grupos, no hubo diferencia estadísticamente significativa. Conclusión: La muestra estudiada es muy variable en cuanto a estructura de microsatélites, incluyendo la presencia de alelos raros, lo que nos permite la oportunidad de describir la población estudiada, lo cual es un paso fundamental en la identificación de implicaciones genéticas en la tumorigénesis de ES

Humans , Male , Oncogenes , Sarcoma, Ewing , Microsatellite Repeats/genetics , Genetic Predisposition to Disease , DAX-1 Orphan Nuclear Receptor
Rev. Investig. Innov. Cienc. Salud ; 4(2): 121-136, 2022. tab, ilus
Article in Spanish | LILACS, COLNAL | ID: biblio-1419007


Introducción. La diabetes mellitus (DM) es una de las enfermedades crónicas más comunes, siendo una de las causas principales de mortalidad de la población mun-dial. La dermatoglifia es empleada como instrumento para el hallazgo de ciertos aspectos biológicos en diferentes poblaciones. Objetivo. Reconocer, a partir de una revisión sistemática, la relevancia que tiene la dermatoglifia como medio de hallazgo de diabetes mellitus. Metodología. Revisión de literatura científica en bases de datos como Sciencedi-rect, PubMed, Scopus y BVS, en las cuales se extrajo información después de co-rrer la ecuación de búsqueda con términos MESH. Posteriormente, fueron revisados para incluir aquellos artículos relacionados con DM y dermatoglifia. Para todo el proceso se siguió la metodología PRISMA, evaluando los artículos con la escala de sesgo de Cochrane y el nivel de evidencia y recomendación con escala SIGN. Resultados. Después de una revisión de 475 artículos, se incluyeron ocho artículos, y al ser evaluados fueron clasificados cinco artículos 2+ y tres 2-, con nivel de reco-mendación D. Conclusión. La dermatoglifía es una herramienta útil como medio de detección de la DM. Sin embargo, es necesario realizar estudios de cohortes para demostrarlo en di-ferentes poblaciones, como la colombiana. En ese sentido, se encuentra que el 70% de los artículos revisados demuestran que la predicción de hallazgo de DM es efectiva. Sin embargo, el 30% de las investigaciones dentro de esta revisión no consideran que sea una herramienta lo suficientemente óptima para descubrir la patología en la población.

Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases, be-ing one of the main causes of mortality in the world population. Dermatoglyphics is used as an instrument for the discovery of certain biological aspects in different populations.Objective. To recognize, by doing a systematic review, the relevance of dermato-glyphics as a means of finding diabetes mellitus. Methodology. Review of scientific literature in databases such as Sciencedirect, PubMed, Scopus, and VHL, in which information was extracted after running the search equation with MESH terms. After that, they were revised to include those articles related to DM and dermatoglyphics. For the entire process, the PRISMA methodology was followed, evaluating the articles with the Cochrane bias scale and the level of evidence and recommendation with the SIGN scale. Results. After a review of 475 articles, eight articles were included, and when evalu-ated, five articles were classified as 2+ and three as 2-, with a level D recommendation. Conclusion. Dermatoglyphics is a useful tool as a means of detecting DM. However, it is necessary to carry out cohort studies to demonstrate this in different populations, such as the Colombian population. 70% of the reviewed articles show that the prediction of DM finding is effective. Nevertheless, 30% of the investigations within this review do not consider it to be a sufficiently optimal tool to discover the pathology in the population

Dermatoglyphics , Diabetes Mellitus , Chronic Disease , Causality , Cohort Studies , Genetic Predisposition to Disease , Medical Subject Headings , Diagnosis , Methodology as a Subject , Systematic Review
Article in English | WPRIM | ID: wpr-928829


BACKGROUND@#This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.@*METHODS@#First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.@*RESULTS@#A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).@*CONCLUSION@#The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.

Humans , Case-Control Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , RNA, Long Noncoding/genetics , Silicosis/genetics