Polymorphism in Genes Encoding Adaptor Proteins ST13 and STIP1 and the Risk of Ischemic Stroke: a Pilot Study.

Adaptor proteins stress induced phosphoprotein 1 (STIP1) and ST13 Hsp70 interacting protein (ST13) may play a crucial role in the pathophysiology of ischemic stroke through controlling protein folding, neuronal survival, and regulation of HSP70/HSP90. The present pilot study investigated whether tagSNPs in genes encoding ST13 (rs138335, rs138344, rs7290793, and rs138344) and STIP1 (rs4980524) are associated with ischemic stroke. DNA samples from 721 ischemic stroke patients and 471 healthy controls were genotyped using the MassArray-4. Our research revealed a relationship between rs138344 ST13 and the risk of ischemic stroke, which was seen only in females (risk allele G; OR=1.34, 95%CI=1.07-1.69; p=0.01). The haplotype rs138335G-rs138344C-rs7290793C ST13 was linked with lower risk of ischemic stroke in females: OR=0.42; 95%CI=0.26-0.68; p=0.0005. Thus, ST13 represents a novel genetic marker for ischemic stroke.

[Studying the association between genetic polymorphism of growth factors and the development of primary open-angle glaucoma]. / Izuchenie assotsiatsii geneticheskikh polimorfizmov faktorov rosta s razvitiem pervichnoi otkrytougol'noi glaukomy.

Primary open-angle glaucoma (POAG) is a multifactorial disease, etiopathogenesis of which largely depends on growth factors. Possessing a variety of medical and biological effects, these cytokines may influence the development and progression of POAG. AIM: to reveal the role of genetic polymorphisms of growth factors in predisposition to developing POAG that is refractory to local hypotensive therapy. MATERIAL AND METHODS: The object of the study were 162 patients with stage II-III POAG, in whom local hypotensive therapy was inefficient, 90 patients with stage II-III POAG well controlled on local hypotensive therapy, and 191 controls. The material for the study was venous blood taken from the cubital vein of a proband. Isolation of genomic DNA was performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of growth factors was performed through allelic discrimination. For that, synthesis of DNA was carried out via polymerase chain reaction (PCR). RESULTS: It is found that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is refractory to local hypotensive therapy. A statistical model for predicting such a risk has been proposed that includes: VEGF-A с.-958C>T genetic marker (rs 833,061), age, concomitant non-inflammatory ocular diseases, microvascular changes in the conjunctiva, the degree of pigmentation of the angle of the anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the model is 90.42%. CONCLUSION: The T IGFR-1 genetic variant and a combination of the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG that is refractory to local hypotensive therapy.

[Association of the -844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers]. / Assotsiatsiya polimorfizma -844G>A gena katalazy s povyshennym riskom razvitiya arterial'noi gipertonii u kuril'shchikov.

AIM: To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH). SUBJECTS AND METHODS: The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay. RESULTS: The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers. CONCLUSION: Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.

[SMOKING AS A TRIGGER FACTOR IN THE DEVELOPMENT OF DIABETIC ANGIOPATHY OF LOWER EXTREMITIES IN MEN WITH METHYLENETETRAHYDROFOLATEREDUCTASE 677TT GENOTYPE].

Enhanced thrombogenesis in patients with diabetes mellitus (D) is related to genetically determined disorders of the blood coagulation system analogous to those associated with hereditary thrombophilia. The aim of this work was to elucidate the relationship between the functionally significant methylenetetrahydroxyfolatereductase (MTHFR) C677T (rs1801133) gene polymorphism and the development of diabetic angiopathy of lower extremities (DALE) in ethnic Russian men residing in Central Russia (mostly Kursk region). The study involved 434 subjects including 50 with DALE and 384 healthy volunteers. All of them were genotypedfor the MTHFR C677T gene polimorphim by real-time PCR with allele discrimination using TaqMan-probes. No significant differences in the frequency of alleles of MTHFR C677T gene polymorphism were documented between the general samples and sex-matched groups. Stratified sex-specific analysis showed that 677TT genotype is associated with increased risk of DALE in smoking men (OR 4.2; 95% CI 1.28-13.79, p=0.01). In non-smoking men the 677TTgenotype was unrelated to the development of this complication. It is concluded that the risk of DALE is determined by the close relationship between genetic (UTHFR gene) and exogenous (smoking) factors which suggests the multifactorial nature of this pathology.

[The combined effect of E298D polymorphism of the endothelial nitric oxide synthase gene and smoking on the risk of cerebral stroke].

Violations of the endothelium-dependent regulation of cerebral vessel tone are an important link in the pathogenesis of cerebrovascular disorders. The purpose of this study was to investigate the association of--86T>C and E298D polymorphisms of the endothelial nitric oxide synthase(NOS3) gene with the risk of ce-ebral stroke (CS) in Russian inhabitants of Central Russia, as well as to evaluate the trigger effect of smoking on the risk of CS in carriers of genotypes NOS3. Genotyping of-786T>C and E298D polymorphisms of the NOS3 gene was carried out through real time. CR and TaqMan allele discrimination assays. It was deter-ined that the genotype 298DD is associated with the risk of CS (OR =-1.71, 95% CII= 1.05-2.78, P= 0.03). Subsequent analysis showed that genotype 298 DD (OR = 3.75; 95% CII= 1.39-10.11; P= 0.01) is associatedw ith an increased risk of CS exclusively in smoking individuals. The combination ofg enotypes -786T/Cx298D/D was associated with the risk of CS. n smokers (OR = 7.71; 95% CI = 1.31-45.34; P = 0.02). In the present study, it was found that smoking is a significant modifying risk factor for cerebral stroke in the carriers of the 298DD and -786T/C. enotypes of endothelial nitric oxide synthase.