The Association Between MKL1-184C>T Gene Polymorphism And Coronary Artery Disease

Background Coronary heart disease (coronary heart diseases, CHD) is a frequently occurring and commonly-seen disease among a serious threat to human health, whose cause has not yet completely clear. Extensive and in-depth research currently carried out shows that the disease is a disease of multiple etiologies; and it presents a pattern that a variety of factors respectively acting on the different aspects. Cambien first reported that angiotensin-converting enzyme (ACE) DD genotype frequency distribution in patients myocardial infarction was significantly higher than the control group in1992, revealed that the genetic factors may be involved in the pathogenesis of coronary heart disease. Since then, researchers from different countries have conducted a lot of research work. With the deepening of the research and development of biology techniques, more and more evidence proved that coronary heart disease had a genetic predisposition. Multiple genes closely related to the susceptibility to coronary heart disease have been found. Megakaryoblastic leukemia factor-1(MKL1) is also called myocardin-related transcription factor-A (MRTF-A), a member of MRTF family. Human MKL1gene is located on chromosome22q13. According to reports, MKL1may have effects on the cardiovascular system formation and maintain process through the regulation of abnormal proliferation of the smooth muscle cells as well as through RhoA and TGF-beta-dependent channels participate in coronary heart disease’s formation and development process. Kunihiko Hinohara etc. in2009first discovered the-184C> T polymorphism of MKL1involved in the pathogenesis of coronary heart disease of Japanese and Korean. Therefore, the relationship between MK.L1gene polymorphism and coronary heart disease cannot be ignored. But now, there are no reports related with the MKL1gene and coronary heart disease in China. Based on this, this study discusses the potential correlation between the MKL1gene polymorphism and the coronary heart disease genetic predisposition of the Chinese Han population of Henan, China.Objective Select Henan Han population as the research object, through the research MKL1-184c> T gene polymorphism and the relationship between the Han population with coronary heart disease in Henan, China to explore genetic susceptibility for coronary heart disease in Henan Han population from the view point of molecular genetics.Methods We performed a case-control study with476unrelated CHD patients and325non-CHD controls. Clinical parameters such as fasting serum cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A (apoA), apolipoprotein B (apoB), lipoprotein a (Lpa), fasting blood glucose and other clinical data were measured. All the patients extracted venous blood in the heparin anticoagulation tube in the morning, using cell genomic DNA extraction kit for genomic DNA extraction. All SNPs were genotyped by using TaqMan SNP genotyping assay.Results The distribution of MKL1-184C>T gene polymorphism was in accordance with the Hardy-Weinberg equilibrium. There was a significant difference in genotypes frequencies between CHD group and the control group (P=0.007). The frequencies of MKL1T allele in CHD group was significantly higher than the control group (38.6%vs30.8%, P=0.001). After logistic regression models adjusted for CHD risk factors, the risk of CHD among CT genotypes was1.765times higher than the CC genotypes (OR=1.765,95%CI:1.246-2.5), and TT genotypes was1.806times than the CC genotypes (OR=1.806,95%CI:1.203-2.71). In a summary, genotypes with at least one T allele (CT or TT genotypes) had a significantly increased CHD risk than the CC genotypes with a ratio of1.78to1(OR=1.780,95%CI:1.311-2.418). There was a close association between-184T allele and3VD (OR:1.614,95%CI:1.259-2.07, P<0.05).Conclusion The-184C> T of MKL1was an important susceptibility locus of CHD in the Han people of Chinese in Henan province, and T allele was probably an independent risk factor for CHD among the Han people in Henan province. The homozygosity for the T allele is not only associated with an increased risk for CHD but also correlated with severity of stenosis in the Chinese Han population.