Список литературы

2658-6533

Научные результаты биомедицинских исследований

2658-6533

10.18413/2658-6533-2024-10-1-0-3

3334

Генетика

Пол-специфические особенности межлокусных взаимодействий, определяющих подверженность к гипертонической болезни

Sex-specific features of interlocus interactions determining susceptibility to hypertension

Иванова

Татьяна Анатольевна

Ivanova

Tatyana A.

ivanova_ta@bsu.edu.ru

2024

10100

Актуальность: Гипертоническая болезнь (ГБ) относится к группе широко распространенных заболеваний как у мужчин, так и у женщин, но при этом заболевание чаще регистрируется (≈20%) у мужчин, чем у женщин Генетические факторы, определяющие гендерные особенности распространенности ГБ в значительной степени не известны. Цель исследования: Установить пол-специфические особенности межгенных взаимодействий GWAS-значимых локусов, определяющих подверженность к ГБ. Материалы и методы: Выборка мужчин включала 564 больных ГБ и 257 контроля (общий объём выборки n=821), женщин – 375 больных ГБ и 209 контроля (общий объём выборки n=584). Выполнено генотипирование 10 полиморфизмов, показавших связи с ГБ (артериальным давлением (АД)) в ранее проведенных полногеномных исследованиях (GWAS). Межгенные взаимодействия, определяющие подверженность к ГБ у мужчин и женщин, оценивались методом MB-MDR. Результаты: У мужчин подверженность к ГБ определяется межлокусным взаимодействием rs932764-PLCE1 × rs7302981-CERS5 × rs1799945-HFE × rs8068318-TBX2 (Wald st. = 32,12 рperm=0,001) с наиболее выраженным эффектом двухлокусного взаимодействия rs1799945-HFE × rs8068318-TBX2 (определяет 0,76% энтропии). Среди женщин наиболее значимой по отношению к ГБ является четырехлокусная модель, включающая полиморфные локусы rs932764-PLCE1 × rs8068318-TBX2 × rs1173771-AC026703.1 × rs167479-RGL3 (Wald st. = 33,53 рperm<0,001) с максимальным вкладом в энтропию заболевания (2,26%) парного взаимодействия rs8068318 TBX2 × rs167479 RGL3. Полиморфизмы rs932764-PLCE1 и rs8068318-TBX2 являются ГБ значимыми как у мужчин, так и у женщин. Заключение: Межгенные взаимодействия GWAS значимых для ГБ локусов являются пол-специфическими.

Background: Hypertension (HT) belongs to a group of widespread diseases in both men and women, but at the same time the disease is more often registered (≈20%) in men than in women. Genetic factors determining the sex characteristics of the prevalence of HT are largely unknown. The aim of the study: To establish sex-specific features of intergenic interactions of GWAS-significant loci determining susceptibility to HT. Materials and methods: The sample of men included 564 patients with HT and 257 controls (total sample size n=821), women – 375 patients with HT and 209 controls (total sample size n=584). Genotyping of 10 polymorphisms that showed associations with HT (blood pressure (BP)) in previously conducted genome-wide studies (GWAS) was performed. The intergenic interactions determining the susceptibility to HT in men and women were evaluated by the MB-MDR method. Results: In men, susceptibility to HT is determined by the interlocus interaction rs932764-PLCE1 × rs7302981-CERS5 × rs1799945-HFE × rs8068318-TBX2 (Wald St. = 32.12 pperm =0.001) with the most pronounced effect of two-locus interaction rs1799945-HFE × rs8068318-TBX2 (determines 0.76% of entropy). Among women, the most significant in relation to HT is the four-locus model, which includes polymorphic loci rs932764-PLCE1 × rs8068318-TBX2 × rs1173771-AC026703.1 × rs167479-RGL3 (Wald St. = 33.53 pperm <0.001) with the maximum contribution to the entropy of the disease (2.26%) of the pair interaction rs8068318-TBX2 × rs167479-RGL3. Polymorphisms rs932764-PLCE1 and rs8068318-TBX2 are very significant in both men and women. Conclusion: The intergenic interactions of HT-significant GWAS loci are sex-specific.

гипертоническая болезньмужчиныженщиныполиморфизмассоциациимежгенные взаимодействияGWAS

hypertensionmenwomenpolymorphismassociationsintergenic interactionsGWAS

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