THE ASSOCIASON OF VITAMIN D RECEPTOR GENE (VDR) POLYMORPHISMS WITH HIGH BLOOD PRESSURE IN STROKE PATIENTS OF UKRAINIAN POPULATION.

OBJECTIVE: The aim: To study the association of the polymorphisms VDR gene with high blood pressure in stroke patients in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 170 patients with atherothrombotic ischemic stroke (AIS) and 124 healthy individuals (control group) was used for genotyping. Four polymorphisms (FokI, BsmI, ApaI, TaqI) of gene VDR were examined with PCR-RFLP methodology. Statistical analysis was performed by using SPSS-17.0 program. RESULTS: Results: The correlation of genotypes of polymorphic variants of FokI, BsmI, ApaI and TaqI of the VDR gene with the development of ischemic atherothrombotic stroke in individuals with normal and high blood pressure was detected. Statistical analysis of the obtained data revealed that among carriers of genotypes F/F, b/b, a/a, a/A, and T/T patients with AI have statistically significantly higher incidence of hypertension than patients in the control group. CONCLUSION: Conclusions: It was found that persons with genotypes F/F, b/b, a/a, a/A, and T/T showed a statistically significant relationship between hypertension and the development of IAS. The application of logistic regression has made it possible to establish that the risk of IAS in people with normal blood pressure and genotype F/f is 3.2 times higher than in normotensive homozygotes for the F-allele.

Association Study between BGLAP Gene HindIII Polymorphism and Type 2 Diabetes Mellitus Development in Ukrainian Population.

Type 2 diabetes mellitus (T2DM) belongs to the diseases with hereditary predisposition, so both environmental and genetic factors contribute to its development. Recent studies have demonstrated that the skeleton realizes systemic regulation of energy metabolism through the secretion of osteocalcin (OCN). Thus, the association analysis between HindIII single nucleotide polymorphism of OCN gene (BGLAP) promoter region and T2DM development in Ukrainian population was carried out. 153 individuals diagnosed with T2DM and 311 control individuals were enrolled in the study. The genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The lack of association between BGLAP HindIII single nucleotide polymorphism (SNP) and T2DM development among Ukrainians was found. Further studies with extended groups of comparison are needed to confirm the obtained results.

Positive Association between EDN1 rs5370 (Lys198Asn) Polymorphism and Large Artery Stroke in a Ukrainian Population.

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.

[The association between enpp1 rs997509 polymorphism and type 2 diabetes mellitus development in ukrainian population].

OBJECTIVE: Introduction: Genome-Wide Association Studies have identified a large number of polymorphic loci associated with type 2 diabetes mellitus (T2DM). Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) gene is one of the candidate genes which have primary importance in T2DM development. Several studies revealed the association between ENPP1 polymorphisms, including rs997509, and T2DM, obesity, insulin resistance and metabolic syndrome in different populations. The aim: To test the association between ENPP1 rs997509 polymorphism and T2DM development in patients with different risk factors in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 317 unrelated T2DM patients and 302 healthy volunteers was used for analysis. ENPP1 rs997509 genotyping was performed using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. RESULTS: Results: Our results revealed that ratio of C/C homozygotes, C/T heterozygotes and T/T homozygotes between case and control groups was significantly different (89.0 % , 11.0%, 0 % vs 94.4 %, 5.6 %, 0 %, P = 0.015). It was shown that risk of T2DM development in T allele carriers is significantly higher compared to C/C homozygotes (OR = 2.086; P= 0.027). Herewith the risk increased in heterozygotes with BMI ≥ 25 kg/m2 (OR = 2.223, P=0.031) and obesity (OR = 3.230; P = 0.023). CONCLUSION: Conclusions: ENPP1 rs997509 polymorphism is associated with T2DM development in Ukrainian population.

G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in 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.

Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis.

OBJECTIVE: The study was designed to assess the effects of polymorphisms in genes associated with essential hypertension on the variation of erythrocyte membrane proteins (EMPs) in hypertensive patients. METHODS: Major EMPs content was analyzed in blood from 1162 unrelated Russians (235 hypertensive patients, 176 healthy controls, and 751 random individuals from the Central Russia population). Essential hypertension patients were genotyped for 11 polymorphisms of essential hypertension susceptibility genes including ADD1 (rs4961), GNB3 (rs5443, rs16932941), NOS3 (rs1799983, rs2070744), ACE (rs5186), AGTR1 (rs5186), AGT (rs699, rs4762), MR (rs5534), and TGFB1 (rs1800471). EMP contents and their relationship with the genetic loci were analyzed using various statistical tests. RESULTS: Sex-specific differences in EMP contents between the cases and controls were observed. Regardless of sex, hypertensives exhibited mainly decreased levels of alpha (SPTA1) and beta-spectrin (SPTB) and increased levels of glucose transporter (GLUT1) as compared with healthy subjects (P ≤ 0.001). EMP correlated differently in essential hypertension patients and controls. Almost 70% of the joint variation in the EMP levels is explained by five gender-specific principal components. The essential hypertension susceptibility genes showed considerable effects on the levels of spectrins and glucose transporter. A joint variation of the genes explained about half the total polygenic variance in the GLUT1, SPTA1, and SPTB levels in hypertensives. CONCLUSIONS: The study showed that essential hypertension susceptibility genes are the important factors of the inherited EMP variation, and their pleitropic effects may be mirrored in the altered expression of genes encoding cytoskeletal proteins and those related to intracellular glucose metabolism.

Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility.

N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines, aromatic amines and hydrazines. The present study was designed to investigate whether two common single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929; 590G>A, rs1799930) are associated with susceptibility to idiopathic male infertility and to assess if the risk is modified by oxidant and antioxidant exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men) were genotyped for the polymorphisms by PCR and restriction fragment length polymorphism. No association was found between the NAT2 polymorphisms and idiopathic male infertility. However, gene-environment interaction analysis revealed that a low-acetylation genotype, 590GA, was significantly associated with increased disease risk in men who had environmental risk factors such as cigarette smoking (OR 1.71, 95% CI 1.02-2.87, P = 0.042), alcohol abuse (OR 2.14, 95% CI 1.08-4.27, P = 0.029) and low fruit/vegetable intake (OR 1.68, 95% CI 1.01-2.79, P = 0.04). This pilot study found, as far as is known for the first time, that the polymorphism 590G>A of NAT2 is a novel genetic marker for susceptibility to idiopathic male infertility, but the risk is potentiated by exposure to various environmental oxidants.

Transforming growth factor beta 1 is a novel susceptibility gene for adolescent idiopathic scoliosis.

STUDY DESIGN: A genetic association study of the transforming growth factor beta 1 (TGFB1) gene with adolescent idiopathic scoliosis (AIS) in Russian population. OBJECTIVE: To determine whether common genetic polymorphisms C-509T (rs1800469) and Arg25Pro (rs1800471) of the TGFB1 gene are associated with susceptibility to AIS. SUMMARY OF BACKGROUND DATA: An importance of growth factors for the pathogenesis of AIS has been demonstrated by the findings of abnormal expression of these proteins in the spine and surrounding tissues in patients with AIS. However, no studies have been performed to investigate the relationship between genetic polymorphisms of the TGFB1 gene and susceptibility to AIS. METHODS: A total of 600 unrelated adolescents from Central Russia (Moscow) were recruited in this study, including 300 patients with AIS and 300 age- and sex-matched healthy adolescents. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The allele -509T and genotype -509TT of the TGFB1 gene were significantly associated with the increased risk of idiopathic scoliosis in both females and males (P < 0.01). Logistic regression analysis has revealed a recessive model of the genetic association between polymorphism C-509T of the TGFB1 gene and AIS. Moreover, we found sexual dimorphisms in the relationships of SNP C-509T of the TGFB1 gene with both the age of disease onset and curve severity: the polymorphism was found to determine both an early onset of scoliosis and the severity of curvature in females but not in males (P < 0.05). CONCLUSION: This study, for the first time, highlights the importance of TGFB1 gene for the development and progress of AIS. We hypothesize several mechanisms by which the TGFB1 gene may contribute to spinal deformity in patients with AIS.

Association of matrix Gla protein gene allelic polymorphisms (G(-7)→A, T(-138)→C and Thr(83)→Ala) with acute coronary syndrome in the Ukrainian population.

BACKGROUND: Several allelic variants of matrix γ-carboxyglutamic acid protein (MGP) can differentially affect the development of certain forms of ischemic heart disease depending on specific characteristics of each population. OBJECTIVE: To study the distribution of allelic variants of MGP promoter T(-138)→C (rs1800802) and G(-7)→A (rs1800801), and Thr(83)→Ala exon 4 (rs4236) polymorphisms in a Ukrainian population of patients with acute coronary syndrome (ACS). METHODS: Polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis were used to detect the above-mentioned variants of the MGP gene in 115 patients with ACS and in 140 essentially healthy individuals. RESULTS: The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of the T(-138)→C MGP promoter polymorphism in patients with ACS were 59.8%, 32.7% and 7.5%, respectively. The corresponding distributions of variants in the control group were 54.0%, 41.0% and 5.0%, respectively (P>0.05 [χ(2) test]). With respect to the G(-7)→A polymorphism, the respective distributions were 42.1%, 45.6% and 12.3%, compared with 50.7%, 45.0% and 4.3% in the control group, respectively (P<0.05). Finally, the respective distributions according to the Thr(83)→Ala exon 4 polymorphism were 42.6%, 43.5% and 13.9%, respectively, compared with 45.3%, 43.0% and 11.7% in the control group. Using logistic regression analysis, it was estimated that the A/A genotype (G(-7)→A polymorphism) was significantly (P=0.02) associated with ACS (OR 4.302 [95% CI 1.262 to 14.673]). CONCLUSION: The allelic A/A promoter variant of MGP G(-7)→A polymorphism can be considered a risk factor for ACS in the Ukrainian population.