There are a lot of convincing evidences about the involvement of endothelin pathway proteins in the pathogenesis of atherosclerosis and its fatal complications. In this study, the analysis of a possible association between EDN1 rs5370 and EDNRA rs5335 gene polymorphisms and the risk of large artery stroke (LAS) in a Ukrainian population was conducted. 200 LAS patients and 200 unrelated controls were enrolled in a case-control study. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used for SNP genotyping. Our results revealed that EDN1 rs5370 polymorphism was associated with LAS development both before and after adjustment for atherosclerosis risk factors (sex, age, body mass index, arterial hypertension, type 2 diabetes mellitus, and smoking). The risk for a LAS incident in rs5370-T allele carriers was 1.6 times higher (CI = 1.066–2.403; P = 0.020) than in subjects with the GG genotype. No link between EDNRA rs5335 and LAS risk in a Ukrainian population was found. The present study indicated that EDN1 rs5370, but not EDNRA rs5335, can be the strong genetic predictor for LAS development in a Ukrainian population.

Vitamin K epoxide reductase complex subunit 1 (VKORC1) is integral 163-amino acid long transmembrane protein which mediates recycling of vitamin K 2,3-epoxide to vitamin K hydroquinone and it is necessary for activation of vitamin K-dependent proteins (VKDPs). Herein, the association between G-1639A (rs9923231) and C1173T (rs9934438) single-nucleotide polymorphisms (SNPs) of the VKORC1 gene and ischemic stroke (IS) was tested in Ukrainian population. Genotyping was performed in 170 IS patients and 124 control subjects (total 294 DNA samples) using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. Our data showed that G-1639A but not C1173T polymorphism was related to IS, regardless of adjustment for age, sex, body mass index, smoking status, and arterial hypertension. The risk for IS in -1639A allele carriers (OR = 2.138, P = 0.015) was higher than in individuals with G/G genotype. Haplotype analysis demonstrated that -1639G/1173T and -1639A/1173C were related to increased risk for IS (OR = 3.813, P = 0.010, and OR = 2.189, P = 0.011, resp.), while -1639G/1173C was a protective factor for IS (OR = 0.548, P < 0.001). Obtained results suggested that -1639A allele can be a possible genetic risk factor for IS in Ukrainian population.

Наведено результати визначення 10 поліморфізмів генів системи матриксного Gla-протеїну (ген MGP-T-138 →С (rs1800802), G-7 →A (rs1800801), Thr 83 →Ala (rs4236); ген VDR-FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), ген GGCX-Arg 325 →Gln (rs699664), ген VKORС1-T 2255 →C (rs2359612), ген BMP-2-Ser 37 →Ala (rs2273073)) у 170 хворих з ішемічним атеротромботичним інсультом (ІАТІ) і 124 здорових індивідуумів (контрольна група). Встановлено, що існує зв'язок між ІАТІ і поліморфними варіантами генів MGP (G-7 →A) та VKORC1 (Т 2255 →С). Ризик розвитку ІАТІ у носіїв мінорного алеля A/A (G-7 →A-поліморфізм) у 2,6 вищий, ніж у носіїв основного алеля (G/A+G/G), а у осіб з генотипом С/С (Т 2255 →С-поліморфізм) у 2,2 раза більший, ніж у гомозигот за основним алелем. Збіг у пацієнтів генотипів T/C і G/G, C/C і G/A, а також генотипу A/A (G-7 →Aполіморфізм) із будь-яким з генотипів за Т 2255 →С-поліморфізмом збільшує ризик розвитку ІАТІ.

⎯The present study was performed to investigate whether common single-nucleotide polymorphism K121Q (rs1044498) of the ENPP1 gene is associated with the known risk factors of atherosclerosis (overweight, dyslipoproteinemia, hypertension, diabetes, smoking, and hypercoagulability) in persons with acute coronary syndrome. Venous blood of 118 patients was genotyped for the polymorphism by PCR and restriction fragment length polymorphism method. In patients divided into two subgroups according to their genotype (KK and KQ + QQ), the statistically significant differences were revealed only for plasma LDL-cholesterol level and fibrinolytic activity. The carriers of minor allele (KQ + QQ) had lower LDL-cholesterol concentration and the time of fibrinolysis than the major allele homozygotes (KK). The division of patients into subgroups according to presence or absence of some risk factors for atherosclerosis showed no statistically significant differences between K121Q genotype distributions for any of the comparison.

THE LINK BETWEEN MTHFR C677T GENE POLYMORPHISM AND TYPE 2 DIABETES MELLITUS DEVELOPMENT IN UKRAINIAN POPULATION