Aim. To reveal the association of hereditary specifics of inflammatory factors with the adverse risk in atrial fibrillation (AF).Material and methods. Totally 258 patients studied (68,5±0,67 y. o.) with nonvalvular AF, recording the events as ischemic stroke, myocardial infarction, venous and arterial thromboembolism. Mean follow-up was 455±11,71 days.Results. Factors that are independently associated with ischemic stroke development in patients not receiving anticoagulants (n=101), were the allele C of polymorphic marker rs2228145(А/С) of gene IL-6 receptor (OR 13,25 CI 1,57112,18, р=0,018), age ?75 y. o. (OR 1,1, CI 1,008-1,2, р=0,032) and EF LV (OR 0,97 CI 0,94-0,99 р=0,027), with a “thrombotic endpoint” development — DM (OR 4,3 CI 1,46-12,45 р=0,008), EF LV (OR 0,96 CI 0,94-0,98, р<0,0001) and carriage of allele C of polymorphic marker rs2228145(А/С) of receptor to IL-6 gene (OR 4,03 CI 1,0715,26, р=0,04). There was no association with adverse outcomes in genes IL-6 polymorphisms as (G(-174)C and G(-572)C), ИЛ-10 (C(-819)T), ФНО (G(-238)A, G(-308)A and ФНО? rs180630). In those receiving adequate anticoagulant therapy (n=157) there was no significant association of IL-6 receptor gene polymorphism with adverse outcomes.Conclusion. Therefore, the carriage of allele C of polymorphic marker rs2228145(А/С) of the IL-6 receptor gene might be an independent risk marker for adverse outcome in non-valvular AF, potentially, being a selection tool for those patients not having enough high risk according to common scores.
To study the distribution of alleles and genotypes of polymorphic markers of genes CYP2C9 and VKORC1 of Russian patients who live in Moscow, and in order to assess the influence of genetic factors on warfarin therapy 400 patients have been genotyped. The dosage of warfarin which is required for achievement of INR target values has been different among owners of different geno- types of polymorphic markers of genes CYP2C9 . Meanwhile the highest average dose has been required for genotype *1/*1 and the lowest – for owners of alleles *2 and *3 . For polymorphism G(- 1639)A of the gene VKORC1 the dosage of warfarin which is required for achievement of the INR target values, has been different among owners of different genotypes. The highest average dose has been required for genotype GG, and the lowest – for genotype AA. The results will allow to work out more accurate algorithm of choosing of the initial dose of warfarin depending on the genotypes of polymorphic markers of genes CYP2C9 and VKORC1.
Для изучения распределения аллелей и генотипов полиморфных маркеров генов CYP2C9 и VKORC1 у русских больных, проживающих в г. Москве, и оценки влияния генетических факторов на терапию варфарином было проведено генотипирование 400 пациентов. Дозировка варфарина, необходимая для достижения целевых значений МНО, различалась у носителей различных генотипов полиморфных маркеров гена CYP2C9 , при этом наибольшая средняя доза требовалась для носителей генотипа *1/*1 , а наименьшая – для носителей аллелей *2 и *3 . Для полиморфного маркера G(-1639)A гена VKORC1 дозировка варфарина, необходимая для достижения целевых значений МНО, различалась у носителей различных генотипов, наибольшая средняя доза требовалась носителям генотипа GG , а наименьшая – носителям генотипа AA . Полученные данные позволят разработать более точный алгоритм выбора начальной дозы варфарина в зависимости от генотипов полиморфных маркеров генов CYP2C9 и VKORC1 .