Association of Flavin Monooxygenase Gene E158K Polymorphism with Chronic Heart Disease Risk.

We studied the relationship between the risk of chronic heart disease and FMO3 gene polymorphism E158K analyzed by PCR and restriction fragment length polymorphism (RFLP) analysis. The homozygous 158KK genotype of FMO3 gene is associated with high risk of chronic heart disease in women, but not in men. FMO3 gene polymorphism E158K is a significant predictor of predisposition to chronic heart disease in women.

[Association of T174M polymorphism of the angiotensinogen gene with the higher risk of cerebral stroke in women].

AIM: To study the association of M235T (rs699) and T174M (rs4762) polymorphisms of the angiotensinogen (AGT) gene with the risk of cerebral stroke (CS) in the Russians of the Central Chernozem Region. MATERIALS AND METHODS: A total of 638 DNA samples obtained from 353 patients with CS and 285 sex- and age-matched healthy individuals were examined. The polymorphisms were genotyped by polymerase chain reaction (T174M) and TaqMan allelic discrimination (M235T) assays. RESULTS: Heterozygous AGT 174TM genotype carriers were found to be at a higher risk for CS (odd ratio (OR) = 1.52; 95% confidence interval (CI), 1.08-2.15; p = 0.02). A gender-stratified analysis showed that the mutant 174M allele (OR = 1.86; 95% CI, 1.14-3.03, p = 0.01) and variant 174TM and 174MM genotypes (OR = 1.86; 95% CI, 1.09-3.20; p = 0.02) were associated with the higher risk of cerebral stroke in women. CONCLUSION: The association of AGT T174M polymorphism with the risk of CS was first found; but the higher risk of the disease in the carriers of variant alleles and genotypes was observed in the women only.

[Catalase gene polymorphism is associated with increased risk of cerebral stroke in hypertensive patients].

Experimental and clinical studies suggest that oxidative stress is an important pathogenetic mechanism of both essential hypertension (EH) and cerebral stroke (CS). In this paper, we investigated, for the first time, the relationship between polymorphisms of two genes for antioxidant defense enzymes such as catalase (CAT) and flavin-containing monooxygenase 3 (FMO3) and the risk of CS in hypertensive patients. DNA samples obtained from 667 unrelated Russian patients with EH (306 patients with CS, and 361 patients without cerebrovascular accidents) were genotyped for polymorphisms -21A>T (rs7943316) of the CAT gene and E158K (rs2266782) of the FMO3 gene. We found that the -21AA CAT genotype is associated with increased risk of CS in hypertensive males (OR = 1.77 95% CI 1.01-3.07). No significant differences in allele and genotype frequencies of the FMO3 E1 58K polymorphism have been revealed between the groups. The association analysis stratified by the environmental risk factors showed that the -21AA CAT genotype increased the risk of CS in male smokers (OR = 2.33 95% CI 1.40-5.40) as well as in male alcohol abusers (OR = 4.29 95% CI 1.22-15.12). In contrast, the variant genotypes such as an -21AT and -21TT of the CAT gene had a protective effect on the risk of CS in EH males with high or moderate physical activity (OR = 0.30 95% CI 0.11-0.83) and in those men who did not have life stresses (OR = 0.51 95% CI 0.28-0.90). The protective effect of the variant genotypes was also observed in high fruit and vegetable consumers (OR = 0.40 95% CI 0.17-0.93). This study is the first to show that the polymorphism -21A>T CAT is associated with increased risk of cerebral stroke in hypertensive men, however, the relationship between the polymorphism and risk of cerebrovascular disease depends on whether the patients have environmental risk factors or not.

[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors].

AIM: To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers. MATERIAL AND METHODS: We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis. RESULTS: Prevalence of 82ST allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele--0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3. CONCLUSION: G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

[Influence of three point mutations in TNF-alpha promoter gene in clinical manifestations and complications of stomach and duodenal ulcer].

The purpose of our study was to investigate whether polymorphisms -238G/A, -308G/A, and -863C/A within the promoter of the TNF-alpha gene are associated with clinical features of gastric and duodenal ulcer disease in a Russian population. DNA samples of 381 unrelated patients with gastric and duodenal ulcer disease and 216 sex- and age-matched healthy controls were used to determine the TNF-alpha gene polymorphisms by PCR-RFLP assay. Logistic regression analysis has revealed significant associations of polymorphism -308G/A with size of ulcerous defect (p=0.03) and intestinal dyspepsia (p=0.05), polymorphism -238G/A with gastric dyspepsia (p=0.04) and reflux-esophagitis (p=0.05), polymorphism -863C/A with perforation of ulcer (p=0.04). The study results highlight impact of the TNF-alpha gene polymorphisms on various clinical features in patients with peptic ulcer disease.

[Polymorphism -930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma].

AIM: To evaluate the link between promotional polymorphism -930A > G of the cytochrome b gene (CYBA) and onset of bronchial asthma; to examine effects of this locus on the risk of the disease development depending on the pro- and antioxidant action of environmental factors. MATERIAL AND METHODS: We studied samples of DNA obtained from 214 healthy individuals and 215 patients with bronchial asthma treated in Regional Kursk Hospital. We used polymerase chain reaction and analysed polymorphism of restriction fragments lengths for genotyping of -930A > G polymorphism of CYBA gene. RESULTS: Incidence of a variant allele -930G of CYBA gene among men with nonallergic bronchial asthma (nBA) was higher than in healthy men (OR 1.95; CI 1.02-3.73; p = 0.04). The homozygous variant genotype -930G/G was associated with a high risk of nBA in males (OR 2.66; CI 1.14-6.20; p = 0.02). In healthy individuals polymorphisms -930A > G and 640A > G were in negative linkage equilibrium (D = -0.057; p < 0.001) while in patients such associations were not registered. Male smokers with genotype -930G/G had the highest risk of nBA (OR 2.86; CI 1.06-7.77; p = 0.04) while non-smokers with this genotype had no risk of the disease (OR 1.50; CI 0.11-19.64; p = 0.70). Males with -930G/G on low or no vegetable diet had the highest risk of nBA (OR 3.11; CI 1.01-9.63; p = 0.04) while regular vegetable eaters had no risk to develop nBA (OR 0.73; CI 0.30-1.82; p = 0.50). CONCLUSION: We were the first to find relations between -930A > G polymorphism of CYBA gene and predisposition to nBA. This association exists in males and depends on the smoking status and vegetable diet.