No abstract

The purpose of the study - to reveal the dependence of the rate of development of liver fibrosis (LF) on genetic factors of hepatitis C virus (HCV) and single nucleotide polymorphisms (SNPs) of the genes of infected people. In the three groups of patients with different rates of development of LF, HCV subtype, viral load, the number of quasi- variant forms and the presence of intergenotype recombinantion, SNPs of human cytokine genes (IL-1ß, IL-6, IL-10, IL-28B, TNF-a , TGF-ß1), hereditary hemochromatosis (HFE), genes involved in the development of endothelial dysfunction (eNOS) and oxidative stress (CYBA) were analyzed. In all groups of patients with HCV subtype 1b prevailed. In the groups with moderate and fast speed of development of LF viral load was revealed to be higher than in the group with the slow development of fibrosis. The number of genetic variants within E2 protein zone in the latter group of patients is characterized to be more than in other groups. Recombinant HCV RNA (2k/1b) was found in the groups with moderate and rapid development of LF. SNP analysis of genes of patients showed a statistically significant relationship between the rapid formation of LF and allelic variants of IL-1ß (-511 TT), IL-10 (-1082 AA), TNF-a (-238 GA or AA) and HFE (S282Y or Y282Y )genes. In other SNPs of analyzed gene there no association with speed of LF was found.

Intergenotype recombinant RF2k/1b of hepatitis C virus was firstly detected in 2002 in the Russian Federation. In our study patients, infected with this recombinant, had high indices of liver fibrosis and did not achieve a sustained viral response to standard double therapy with exception of one participant. There are discussed and proposed options for treatment and diagnosis of these patients.

Aim. To evaluate association of clinical and genetic factors with left ventricle hypertrophy (LVH) in patients with arterial hypertension (HT).Materials and methods. 672 patients with HT were involved, aged 50,6 y.o. in average, men 67%. Laboratory assays, ECG, echocardiography were performed. Control group included 184 healthy persons. Genotyping with single-nucleotide substitutions of the endothelial NO synthase (eNOS) Glu298Asp gene, the C242T of the NADPH oxidase p22phox subunit and the angiotensin 2 receptor type 1 А1166С gene was carried out using a polymerase chain reaction (PCR) with evaluating of restriction fragments length polymorphism, while with substitutions of the angiotensinogen М235Т, G(-6)A gene allele-specific PCR "in real time" was applied.Results. LVH was found in 39% of patients. It was more frequent in persons above 50 years old (OR 2,8, р<0,0001), in men (OR 1,43, p=0,035), in HT of degree 2-3 (OR 3,35, р<0,0001), HT duration more than 5 years (OR 2,52, р<0,05), in obesity (OR 1,57, р=0,005) or diabetes (OR 3,33, р<0,0001) presence. At genetic factors evaluation decrease of LVH risk was revealed in persons with the MM polymorphism of the angiotensinogen М235Т gene (OR 0,506, р=0,0187). Association of the MM genotype with LVH risk lowering was more obvious at the young age (OR 0,31, р=0,018). The A allele of the eNOS gene Glu298Asp polymorphism increased risk of LVH development when HT was diagnosed in the young age (OR 1,98, р=0,037) and in women up to 50 years old (OR 2,34, р=0,027). The T allele of the p22phox NADPH oxidase gene С242Т polymorphism correlated with LVH risk reduction in HT patients up to 50 years old (OR 0,6, p=0,01), the C allele -with increase of it (OR 1,66, р=0,01), this influence was more noticeable in women up to 50 years old (T allele -OR 0,21; C allele -OR 4,57, p=0,001). Conclusion. Hypertensive LVH correlates with age, male gender, HT degree and duration, obesity and diabetes mellitus. Genetic factors were less associated with LVH. Цель. Анализ ассоциации клинических и генетических факторов с гипертрофией левого желудочка (ГЛЖ) у пациентов с артериальной гипертонией (АГ). Материал и методы. Обследованы 672 пациента АГ, средний возраст 50,6 лет, мужчин 67%. Выполнялись лабораторные исследования, ЭКГ, эхокардиография. Группу контроля состави-ли 184 человека. Генотипирование по однонуклеотидным заменам Glu298Asp гена эндотелиальной NO синтазы, С242Т субъединицы p22phox NADPH оксидазы и А1166С гена рецептора 1 типа к ангиотензину 2 проводилось методом полимеразной цепной реакции (ПЦР) с анализом полиморфизма длины рестрикционных фрагментов, а по заменам М235Т, G(-6)A гена ангио-тензиногена с помощью аллель-специфичной ПЦР «в реальном времени». Результаты. ГЛЖ диагностирована у 39% больных, чаще в возрасте старше 50 лет (ОШ 2,8, р<0,0001), у мужчин (ОШ 1,43, р=0,035), при наличии 2-3 степени АГ (ОШ 3,35, р<0,0001), давности АГ более 5 лет (ОШ 2,52, p<0,05), при наличии ожирения (ОШ 1,57, р=0,005), сахарного диабета (ОШ 3,33, р<0,0001). При анализе генетических факто...