Detection Of C5L2Gene Rare Mutation And Its Association With Coronary Artery Disease

Objective: C5L2, a G protein-coupled7-transmembrane domain complement, hasbeen demonstrated to be a functional receptor of acylation-stimulating protein (ASP),which is a stimulator of triglyceride synthesis or glucose transport. In this study, we willinvestingate the variations in the coding region of the C5L2gene (C698T and G901A)and their association with coronary artery disease (CAD). Methods: We identified novelsingle nucleotide polymorphisms (SNPs),(C698T and G901A) in exon2using apolymerase chain reaction direct-sequencing method. We examined the role of this SNPfor CAD using two independent case-control studies: one was in the Han population (492CAD patients and577control subjects) and the other was in the Uygur population (319CAD patients and554control subjects). Results: Using a polymerase chain reactiondirect-sequencing method. We identified novel single nucleotide polymorphisms (SNP),698C＞T (P233L), and G901A(A300H) in exon2. C698T causes the amino-acid orderfrom proline to leucine at codon233. G901A causes the amino-acid order from Arginineto glutaminate at codon300. We examined the role of C698T for CAD using twoindependent case–control studies: one was in the Han population (492CAD patients and577control subjects) and the other was in the Uygur population (319CAD patients and554control subjects). Heterozygote carriers of the698CT genotype were more frequentamong CAD patients than among controls not only in the Han population (7.3%versus1.7%) but also in the Uygur population (4.7%versus1.6%). The odds ratio (OR) forcarriers of the698CT genotype for CAD was4.484(95%confidence interval (CI):2.197-9.174) in the Han group and2.989(95%CI:1.292–6.909) in the Uygur population.After adjustment of confounding factors such as sex, age, smoking, alcohol consumption,hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol,high-density lipoprotein, the difference remained significant in the Han group (OR＝ 6.604,95%CI:2.776–15.711, P﹤0.001) and in the Uygur group (OR＝2.602,95%CI:1.015–6.671, P＝0.047). We also examined the role of G901A for CAD using twoindependent case-control studies: one was in the Han population (492CAD patients and577control subjects) and the other was in the Uygur population (319CAD patients and554control subjects). Heterozygote carriers of the698CT genotype were more frequentamong CAD patients than among controls not only in the Han population (8.3%versus1.8%) but also in the Uygur population (5.2%versus0.9%). The OR for carriers of the698CT genotype for CAD in the Uygur population was0.172. After adjustment ofconfounding factors such as sex, age, smoking, alcohol consumption, hypertension,diabetes, as well as serum levels of triglyceride, total cholesterol, high-density lipoprotein,the difference remained significant in the Han group (P<0.001) and in the Uygurgroup(OR＝0.172，95%CI:0.052-0.569).Two haplotypes in the Han population in theresult analysis, which the C-A haplotype frequencies in the CHD group was significantlylower than the control group, a statistically significant difference (χ~2＝22.713, P＜0.001),the T-A haplotype distribution in theThe CHD group was significantly higher, thedifference was statistically significant (χ~2＝19.022, P＜0.001). In Uighur population.Analysis of the T-A haplotypes frequency in case group(0.025) was significantly higherthan that of the control group (0.008), the difference was statistically significant (P＝0.004); C-G haplotypefrequency in CAD group (0.005) was significantly lower than thecontrol group (0.026), the difference statistically was significant(P＝0.001). Conclusion:(1) two mutations of C5L2gene (C698T and the G901A) in Han and Uygur populationare association with coronary heart disease;(2) C5L2gene C698T heterozygous genotypemay be a risk factors of coronary heart disease in Xinjiang Han and Uighurs population;G901A heterozygous genotype may be protective factors of coronary heart disease in Hanand Uigur population;(3) the C5L2genes C-G haplotype may be protective factors ofcoronary heart disease in Han population in Xinjiang, a single T-G ploidy may be riskfactors for coronary heart disease in Han population in Xinjiang;(4) the C5L2genes C-Ahaplotype may be protective factors of coronary heart disease in Xinjiang Uygurpopulation, T-G haploid may be risk factors of coronary heart disease in Xinjiang Uygurpopulation.