ПОИСК МАРКЕРОВ РИСКА РАЗВИТИЯ ПАТОЛОГИИ ГЕПАТОБИЛИАРНОЙ СИСТЕМЫ НА ОСНОВЕ ИЗУЧЕНИЯ ГЕНЕТИЧЕСКОГО ПОЛИМОРФИЗМА ГЕНОВ СИСТЕМЫ ДЕТОКСИКАЦИИ КСЕНОБИОТИКОВ

The aim of this study was to compare the frequencies of genotypes and alleles of polymorphic variants of the CYP2E1 and GSTA1 genes in patients with hepatobiliary system pathology who were examined at the Ufa Scientific Research Institute of Occupational Medicine and Human Ecology and healthy individuals living in the Republic of Bashkortostan who have no hepatobiliary system pathology.Materials and methods: 81 patients with pathology of the hepatobiliary system and 502 practically healthy individuals living in the Republic of Bashkortostan were examined. The material for molecular genetic analysis was DNA samples isolated from the peripheral venous blood of the examined individuals by phenol-chloroform extraction. The study of polymorphic loci of the CYP2E1 and GSTA1 genes was carried out by the method of polymerase chain reaction of DNA synthesis. Mathematical processing of the results of the study was carried out using the statistical program Statistics.Results. A comparative analysis revealed statistically significant differences between the group of patients with ASD and healthy individuals in the frequency distribution of the genotypes of the polymorphic locus rs3957357 of the GSTA1 gene. The AA genotype was more common in patients with ASD with a frequency of 16.05%, compared with the control group –8.37% (χ2 = 3.96; p = 0.047). Conclusion As a result of the study, it was shown that the AA genotype (OR = 2.09; 95% CI 1.07 - 4.10) of the polymorphic locus rs3957357 of the GSTA1 gene is a marker of the risk of pathology of the hepatobiliary system.El objetivo de este estudio fue comparar las frecuencias de genotipos y alelos de variantes polimórficas de los genes CYP2E1 y GSTA1 en pacientes con patología del sistema hepatobiliar que fueron examinados en el Instituto de Investigación Científica de Medicina Ocupacional y Ecología Humana de la Ufa e individuos sanos que viven en el República de Bashkortostán que no tienen patología del sistema hepatobiliar.Materiales y métodos: se examinaron 81 pacientes con patología del sistema hepatobiliar y 502 individuos prácticamente sanos que viven en la República de Bashkortostán. El material para el análisis genético molecular fue muestras de ADN aisladas de la sangre venosa periférica de los individuos examinados mediante extracción con fenol-cloroformo. El estudio de los loci polimórficos de los genes CYP2E1 y GSTA1 se llevó a cabo mediante el método de reacción en cadena de la polimerasa de la síntesis de ADN. El procesamiento matemático de los resultados del estudio se realizó mediante el programa estadístico Statistics.Resultados Un análisis comparativo reveló diferencias estadísticamente significativas entre el grupo de pacientes con TEA y los individuos sanos en la distribución de frecuencia de los genotipos del locus polimórfico rs3957357 del gen GSTA1. El genotipo AA fue más común en pacientes con TEA con una frecuencia de 16.05%, en comparación con el grupo control –8.37% (χ2 = 3.96; p = 0.047). Conclusión Como resultado del estudio, se demostró que el genotipo AA (OR = 2.09; IC del 95%: 1.07 - 4.10) del locus polimórfico rs3957357 del gen GSTA1 es un marcador del riesgo de patología del sistema hepatobiliar.Целью данного исследования явилось изучение частот полиморфных вариантов генов СYP2E1 и GSTA1 у больных с патологией гепатобилиарной системы, проходивших обследование в ФБУН «Уфимский НИИ медицины труда и экологии человека» и здоровых индивидов, проживающих в Республике Башкортостан, которые не имеют заболеваний гепатобилиарной системы. Также проводился анализ возможных ассоциаций генотипов этих генов с развитием патологии гепатобилиарной системы.Материалы и методы. Обследован 81 пациент с патологией гепатобилиарной системы и 502 практически здоровых индивида, проживающих на территории Республики Башкортостан. Проведен анализ ассоциаций полиморфных вариантов генов СYP2E1 и GSTA1. Материалом для молекулярно-генетического анализа служили образцы ДНК, выделенные из лимфоцитов периферической венозной крови обследуемых индивидов методом фенольно-хлороформной экстракции. Изучение полиморфных локусов генов СYP2E1 и GSTA1 проводилось методом полимеразной цепной реакции синтеза ДНК. Математическую обработку результатов исследования проводили с использованием статистических программы Statistica.Результаты. Сравнительный анализ выявил статистически достоверные различия между группой больных с патологией гепатобилиарной системы и здоровыми индивидами в распределении частот генотипов полиморфного локуса rs3957357 гена GSTA1. Генотип АА чаще встречался у больных с патологией гепатобилиарной системы с частотой 16,05%, по сравнению с группой контроля–8,37% (χ2=3,96; р=0,047). Заключение. В результате проведенного исследования было показано, что маркером риска развития патологии гепатобилиарной системы является генотип АА (OR=2,09; 95% CI 1,07 – 4,10) полиморфного локуса rs3957357 гена GSTA1

Genetic Polymorphisms of Cytochromes P450 in Finno-Permic Populations of Russia

Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, endogenous hormones, and drugs, including those used in COVID-19 treatment. Cytochrome p450 genes are linked to the pathogenesis of some multifactorial traits and diseases, such as cancer, particularly prostate cancer, colorectal cancer, breast cancer, and cervical cancer. Genotyping was performed on 540 supposedly healthy individuals of 5 Finno-Permic populations from the territories of the European part of the Russian Federation. There was a statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; data on the rs3892097 locus of the CYP2D6 gene shows that Izhemsky Komis are different from the Mordovian and Udmurt populations

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)