IL8 And It's Receptors Genes Polymorphisms And Risk Of Coronary Heart Disease In Norhern Chinese Han Population

Objective: 1. To build up the SNPs catalogue of IL8, IL8RA, IL8RB genes in Northern Chinese Han population. 2. Selecting the representative single nucleotide polymorphisms(SNPs) and checking the genotypes of them in case and control sujects, based on the first partial experiment, in order to investigate the risk between the SNPs and haplotypes of the three genes and the risk of CHD, which is aimed to offer valuable genetic proofs for early diagnosis, prevention and personal treatment of CHD.Methods: This is a case-control study. The subjects erolled in this study were derived from the Northern Chinese Han population and the means of DNA sequencing, polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used to screen the distribution of SNPs and genotypes, allelic frequence, in order to build up the SNPs catalogue of IL8, IL8RA, IL8RB genes.The 48 DNA samples used to screen the SNPs were chosen randomly from the patients who have no sibship among them admitted in cardiology department of the general hospital of Shenyang Military Region. 5'area(<2kb), 5'UTR, coding area, patial introns between extrons, 3'UTR, 3'area(<2kb) were screened by derectly sequencing. The genotypes of 412 subjects in this study were screened by derectly sequencing or PCR-RFLP. SPSS software was used to analyze the difference of SNPs between the CHD and control groups, and a binary logistic-regression analysis was used to check the independent relationship between the SNPs and CHD.Results: 1. 10 SNPs were identified at the area of 9253bp in the three genes, and one among them is identified for the first time. 2. The genotype frequencies of IL8 gene +394G/T have no significant difference between CHD and control gruoups (P >0.05). While the allelic frequencies of the IL8 gene +394G/T polymorphism between the two groups are signigicantly different(P =0.017). The genotype frequencies and allelic frequencies of the IL8 gene +781C/T polymorphism between the two groups are signigicantly different(P=0.035; P=0.037). After adjustment for conventional risk factors, including age, smoking status, hypertension, diabetes mellitus, hypercholesterolemia, a binary logistic-regression analysis suggested that differences were still exist between two groups. The genotypes and allelic frequences of IL8 gene -251A/T, IL8RB +1235T/C polymorphisms have no significant difference between CHD and control groups. 3. Linkage disequilibrium (LD) test and haplotype analysis indicated that there were AGC, AGT, ATC, ATT, TGC, TGT, TTC, TTT haplotypes, no haplotypes significantly increased the risk of CHD.Conclusion: IL8 gene +394G/T, +781C/T polymorphisms may be the independent risk factors of CHD in Northern Chinese Han population. IL8 gene -251A/T, IL8RB+1235T/C polymorphisms may not be independent risk factors.