Associations Of Variants Of Antioxidant Enzymes’ Genes And Renalase Gene With Diabetic Vascular Complications

Type2diabetes is a complicated disease involved in several susceptibility genes.The vascular complications of diabetes including diabetic nephropathy and diabeticcardiovascular disease which were main cause of mortality and morbidity.Therefore, our study focused on:1)associations of three antioxidative genes’variations with diabetic cardiovascular complications which are Val16Ala inManganese superoxide dismutase, Pro198Leu in glutathione peroxidase-1and-262C/T in catalase;2)relationship of variation in renalase gene(Asp37Glu) withdiabetic nephropathy.1) Association of antioxidative genes with diabetic cardiovascular complicationsMnSOD, GPx-1and CAT provide the primary antioxidant defensesystem.Impaired antioxidant defense increases oxidative stress and contributes to thedevelopment of type2diabetes and diabetic cardiovascular disease (CVD). Wepreformed a case-control study in168Chinese type2diabetes patients which weredivided into the non-CVD group (n=83,>10yr since diagnosis) and CVD group(n=85, history of ischemic CVD) to investigate the association of MnSOD Ala16Val,GPx-1Pro198Leu and CAT-262C/T functional polymorphisms with the developmentof diabetic CVD. Genotyping was performed using PCR-restriction fragment lengthpolymorphism (PCR-RFLP) or PCR-based direct sequencing.Results:1) Thegenotypic distribution in the non-CVD and CVD groups and the clinical parameters ingenotypic groups were not significantly different in the three polymorphic sitesrespectively（P>0.05, for each）.2)Among eight genotypic combinations, the mostcommon TT+CC+CC genotype was associated with higher triglyceride levels than allnon-TT+CC+CC genotypes(（1.77±0.12vs.1.43±0.11, p<0.05）). In the CVD group,significantly elevated triglyceride levels were also observed in patients withTT+CC+CC compared to patients with TT+CT+CC or non-TT+CC+CC genotypes.2) Association of RNLS-Asp37Glu with diabetic nephropathyRenalase is a flavin adenine dinucleotide-dependent protein which plays a role indegradation of serum catecholamine concentrations, regulation of hypertention andheart rate. rs2296545, locating in the functional gene region of RNLS, is the only non-synonymous coding SNP, which can lead to amino acid change and furtherdecrease activity of renalase. Several studies reported that renalase can protectkidney by reducing injury of ischemia/reperfusion and. associated with type1diabetes and type2diabetes. However, there is no report on the association withdiabetic nephropathy. We preformed a case-control study in4groups, controlswithout diabetes(Non-DM, n=299), diabetes without nephropathy (DN0，n=215）,diabetes with microalbuminuria（DN1，n=78）and diabetes with massive proteinuriaand hemodialysis treatment（DN-ESRD，n=113）. Genotyping was performed usingTaqman probe to investigate association of rs2296545with the development ofdiabetic nephropathy. Results: genotype-phenotype study indicate the association ofGG genotype with hypention（p=0.003）.2）Differences of genetypic distributionand allelic frequency in DN0, DN1and DN-ESRD were not significant（p>0.05，foreach）.3）genotype of CG+GG was associated with hypention in Non-DM（p=0003、p=0.027）。4）No association was found between rs2296545and diabetes or diabeticnephropathy.