Correlation Between Single Nucleotide Polymorphisms Of ACTA2Promoter Region And Coronary Artery Lesion In Type2Diabetes Patients

Background：Incidence of coronary heart disease and mortality associated with type2diabetes is onthe rise. Therefore, this type coronary heart disease has become the focus of the public healthproblems.Alpha actin encoded by ACTA2gene is the symbol protein of the contracting vascularsmooth muscle cells. The transformation of vascular smooth muscle cells from contractilephenotype to synthetic phenotype plays a very important role in coronary artery lesions. It hasbeen found that transformation of vascular smooth muscle cells from contractile phenotype tosynthetic phenotype accompanied by vascular smooth muscle cell proliferation and migration,and the content of alpha actin and its transcriptional expression of mRNA were significantlyreduced. Therefore, ACTA2gene is particularly important for the coronary arteryatherosclerosis lesions. By the vascular pathological analysis and the cultivation of thevascular smooth muscle cells in vitro, Guo etc found that ACTA2gene mutation carriers aresusceptible to vasodilation or vascular blockage caused by a variety of vascular disease.It has been found that a variety of gene single nucleotide polymorphisms (SNPs, singlenucleotide polymorphisms) of coronary artery heart disease risk factors, such as adipo-nectin、tumor necrosis factor-α (TNF-α), can increase the risk of cardiovascular disease intype2diabetes mellitus patients. Whether are there any similar SNPs(single nucleotidepolymorphisms) in ACTA2promoter region？ We speculate that some SNPs in ACTA2promoter region may regulate the transcription of alpha actin, which can transform thevascular smooth muscle cells phenotype by changing the alpha actin content. And vascularsmooth muscle cell proliferation and migration may participate in the coronary artery lesiondevelopment. It is probable that there is some association between these SNPs and coronaryartery lesions in type2diabetes mellitus patients. Coronary artery lesions induced by Serum insulin remains controversial now. Whetherdoes serum insulin interact with these SNPs in coronary artery lesions process in type2diabetes mellitus patients?Objective：To confirm the speculation that there is some association between these SNPs in ACTA2gene promoter region and coronary artery angiography lesions in type2diabetes mellituspatients and that serum insulin interacts with these SNPs in coronary artery lesions process intype2diabetes mellitus patients.Methods：Eight eligible SNPs loci screened from ACTA2gene promoter region were distributedinto four gene segments which primers and sequencing primers were designed andcompounded;According to the inclusion criteria and exclusion criteria, we selected251patients withtheir clinical and laboratory information and then divided them into case group and controlgroup by coronary angiography results;Peripheral venous blood from every objects was collected to extract genomic DNA bytraditional method called salting out;Four gene sections were sequenced after PCR amplification and recycling of PCRproducts.Result：Only rs1324551loci nucleotide polymorphism distribution, of the8SNPs, wassignificant different between the case group and the control group （P<0.05）.the frequency of G allele and GG genotype of rs1324551loci in the case group and thecontrol group were61.9%、52.4%and39.9%、25.3%respectively in turn. The frequency of Gallele and GG genotype of rs1324551loci in the case group was apparently higher than that inthe control group(P=0.044、P=0.001）. The frequency of G allele and GG genotype ofrs1324551loci was not different between LCA-and LCA+groups （P＞0.05）.After deducting confounding risk factors, in additive and recessive models, the oddsratios of the GG genotype were2.93[95%confidence interval (CI),1.05-8.19; P=0.04] and2.34(95%CI,1.09-5.02; P=0.03) respectively and this correlation was represented only inobjects with low insulin levels. Of the cases group, up to65.5%type2diabetes patients had more than three coronarylesions.In recessive models, the odds ratios of the aging and smoking were1.06（95%CI1.02～1.20, P=0.007）、10.59（95%CI1.27～88.11, P=0.03), but the odds ratios of other traditionalrisk factors were not found.Conclusion：Rs1324551locus of the single nucleotide polymorphism has correlation with degree ofcoronary artery stenosis while without diffusion of coronary artery lesions.The correlation between rs1324551locus of the single nucleotide polymorphism anddegree of coronary artery stenosis was only represented in low insulin level group, whichindicated that the serum insulin may has protection effect in coronary artery stenosis lesions.Coronary lesions were diffuse in patients with type2diabetes and coronary heart disease,and, aging and smoking can independently increase the risk of coronary artery lesions in type2diabetes patients.