Association of Т174М polymorphism of the angiotensinogen gene with the higher risk of cerebral stroke in women


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Abstract

AIM. To study the association of M235T (rs699) and T174M (rs4762) polymorphisms of the angiotensinogen (AGT) gene with the risk of cerebral stroke (CS) in the Russians of the Central Chernozem Region. MATERIALS AND METHODS. A total of 638 DNA samples obtained from 353 patients with CS and 285 sex- and age-matched healthy individuals were examined. The polymorphisms were genotyped by polymerase chain reaction (T174M) and TaqMan allelic discrimination (M235T) assays. RESULTS. Heterozygous AGT 174TM genotype carriers were found to be at a higher risk for CS (odd ratio (OR)=1.52; 95% confidence interval (CI), 1.08-2.15; p=0.02). A gender-stratified analysis showed that the mutant 174M allele (OR=1.86; 95% CI, 1.14-3.03, p=0.01) and variant 174TM and 174MM genotypes (OR=1.86; 95% CI, 1.09-3.20; p=0.02) were associated with the higher risk of cerebral stroke in women. Conclusion. The association of AGT T174M polymorphism with the risk of CS was first found; but the higher risk of the disease in the carriers of variant alleles and genotypes was observed in the women only.

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Ассоциация полиморфизма Т174М гена ангиотензиногена с повышенным риском развития мозгового инсульта у женщин. - Резюме. Цель исследования. Изучение ассоциации полиморфизмов M235T (rs699) и T174M (rs4762) гена ангиотензиногена (AGT) с риском развития мозгового инсульта (МИ) у русских жителей Центрального Черноземья. Материалы и методы. Исследовали 638 образцов ДНК 353 пациентов с МИ и 285 здоровых индивидуумов соответствующего пола и возраста. Генотипирование полиморфизмов проводили методами полимеразной цепной реакции (T174M) и аллельной дискриминации с помощью TaqMan-зондов (M235T). Результаты. Выявлено, что у носителей гетерозиготного генотипа 174TM гена AGT повышен риск развития МИ (отношение шансов - ОШ - 1,52 при 95% доверительном интервале - ДИ - от 1,08 до 2,15; р=0,02). Стратифицированный анализ по полу показал, что мутантный аллель 174M (ОШ 1,86 при 95% ДИ от 1,14 до 3,03; р=0,01), а также вариантные генотипы 174TM и 174MM (ОШ 1,86 при 95% ДИ от 1,09 до 3,20; р=0,02) ассоциированы с повышенным риском развития МИ у женщин. Заключение. Впервые обнаружена связь полиморфизма T174M гена AGT с риском развития МИ, но повышенный риск развития заболевания у носителей вариантных аллелей и генотипов наблюдается только у женщин.
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