| Objective: C5L2, a G protein-coupled 7-transmembrane domain complement, has been demonstrated to be a functional receptor of acylation-stimulating protein(ASP), which is a stimulator of triglyceride synthesis or glucose transport. In this study, Complement 5a receptor(C5a R) was demonstrated a receptor of complement 5a(C5a) which is involved in many inflammatory diseases. The functional responses attributed to C5 a result from its interaction with its receptors C5 a R, which stimulates food intake, play a role in increasing the inflammatory response in adipose tissue as well as the cardiovascular and neural systems. We will investingate the variations in the coding region of the C5L2 gene(754C>A, 602 G>A) and tag SNPs association with coronary artery disease(CAD) and prognosis of coronary artery disease。And then to find the C5 a R1 gene 547G>A and its tag SNPs association with coronary artery disease(CAD) and prognosis of coronary artery disease(CAD). Methods:(1) We use a polymerase chain reaction direct-sequencing method to detect the patient with CAD( there was 48 Han CAD patients and 48 Uygur patients), amplificate the promoter and coding loci of C5L2 gene and C5 a R1 gene, use the Chromas software and DNAMan software under the sequencing results and hit sequence contrast, will find that the single nucleotide polymorphism(SNP) loci in human genome database has carried on the comparison, as in the Hap Map genome database, NCBI/SNP database and Japan were not found in the database this SNP, so we newly identified as new SNPs.(2) A case-control study including 1364 cases with coronary heart disease confirmed by coronary angiography and 1589 gender-, age-, and ethnic-matched controls was desighed to analyse the relationship between C5L2 SNPs and CAD. Genotyping was undertaken using the Taq Man SNP genotyping assay. 374 patients were fellow-up for one year, weobserved the relationship between different genotype and prognosis of coronary heart disease.(3)A case-control study was designed to observe the relationship between genetic polymorphisms of C5 a R1 and prognosis of coronary artery dieases. 1364 patients with coronary heart disease and 1589 control subjects were detectived by the Taq Man SNP genotyping assay. 374 patients were fellow-up for one year, we observed the relationship between different genotype and prognosis of coronary heart disease. Results:(1) We identified two novel SNPs in C5L2, 754C>A and 602G>A in exon 2. This nucleotide change causes the amino-acid order from GCG to GCA at codon 199 and from CCC to CCA at codon 248. a novel SNPs in C5 a R1 547G>A in exon 2. This nucleotide change causes the amino-acid order from GCC to ACC at codon 183(Alanine replacement for threonine), This is a missense mutation.(2) 754C>A of C5L2 gene was associated with coronary artery disease in Uygur ethnic in Xinjiang. CC genotype significantly increased the risk of coronary heart disease, After adjustment of confounding factors such as sex, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, highdensity lipoprotein, 754C>A gene polymorphism was still independent risk factors for coronary heart disease; 754C>A gene polymorphism significantly affected the severity and extent of CAD coronary arterial stenosis. the tag SNP rs2972607 additive model(AG vs AA + GG) and rs8112962 additive model(CT vs TT + CC) was association with CAD in Han and Uygur population. After adjustment of confounding factors, the difference remained significant in the Han group(OR = 1.489, 95% confidence interval [CI]:1.082~2.050, P=0.015 和 OR = 1.556 95%CI:1.111~2.207, P=0.010).(3) 547 G > A in C5 a R1 gene was associated with coronary artery disease in both Han ethnic and Uygur ethnic in Xinjiang. AA genotype significantly increased the risk of coronary heart disease in Han and decreased the risk of coronary heart disease in Uygur. After one year follow-up, by COX multivariate regression analysis showed that after adjusting for other factors the 547 G > A AA polymorphism is an independent risk factor of cardiovascular adverse events in coronary heart disease of Han. There was not association of 547G>A AA polymorphism with adverse prognosis of coronary heart in Uygur. Conclusion:(1)We use a polymerase chain reaction direct-sequencing method to detect the patient with CAD identified two novel SNPs in C5L2, 754C>A and 602G>A in exon 2, a novel SNPs in C5 a R1 547G>A in exon 2.(2) 754C>A gene polymorphism of C5L2 was associated with coronary heart disease in Uygur ethnic, and affect significantly ed the severity and extent of CAD coronary arterial stenosis.(3) 547G>A genepolymorphism of C5 a R1 was associated with coronary artery disease in both Han ethnic and Uygur ethnic in Xinjiang. 754C>A AA genotype is an independent risk factor of cardiovascular adverse events in coronary heart disease of Han. |
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