Association Of 1277T>C Polymorphism In The Complement Factor H Gene With Unstable Angina Pectoris

Background and Objective There is increasing evidence that one of the key factors generating and maintaining inflammation in the arterial intima is the complement system. Inflammation plays an important role in coronary artery disease (CAD) and artherosclerosis (AS). Complement inhibitor factor H (CFH) is a impotent plasma protein which is essential in the regulation of the alternative complement pathway, and plays a critical role in the protection of host vascular cells and endarterium tissues from damage by excessive complement activation, and plays a major role in negative regulation for inflammation. CFH 1277T>C gene polymorphism is a single nucleotide polymorphism in the CFH gene, a 1277T-C transversion, resulting in a tyr402-to-his substitution of the CFH production, which reduces the affinity of CFH for C3b and weaken its inhibition of the complement activation and its ant-atherosclerotic effect.There are some overseas studies have reported that CFH 1277T>C SNP is associated with coronary heart disease, but fewer in domestic. In our study, we investigate the association of the CFH 1277T>C polymorphism and unstable angina pectoris(UAP) in Hunan Han population, and discuss the pathogenesis of coronary heart disease in inflammatory factor and genetic polymorphism, which provides theoretical basis for the diagnosis and gene therapy of coronary heart disease.Method The frequency distribution of the genotypes and alleles of 1277T>C single nucleotide polymorphisms (SNP) of CFH was detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 150 cases with UAP and 146 normal controls of Hunan Han. Age, gender, smoking history, blood lipids, blood glucose, blood pressure levels and body mass index were observed in the study. Statistical analysis was carried out by SPSS 13.0 software.Results 1. In the health control group, the frequencies of CFH 1277T>C genotypes are TT(89.7%), TC(8.2%), CC(2.1%), and the allele frequencies for T and C alleles are 93.8% and 6.2%,respectively. 2. In the UAP case group, the frequencies of CFH 1277T>C genotypes are TT(74.0%), TC(22.7%), CC(3.3%), and the allele frequencies for T and C alleles are 85.3% and 14.7%,respectively.3. Obvious frequency distribution difference of genotypes and alleles in CFH 1277T>C was observed between the UAP and the control groups(P=0.02 and P=0.01), and the difference of the frequency of the CFH 1227C allele carriers(TC+CC genotypes) between the two groups was statistically significant(OR,3.06, 95%CI:1.60-5.86,P<0.01).4. No significant difference in diabetes, hypertension, triglycerides and low density lipoprotein between two groups, while there are significant difference in smoking history, body mass index, total cholesterol and high density lipoprotein.Conclusions It is suggested that CFH 1277T>C SNP is significantly associated with UAP in Hunan Han population. The gene polymorphism may be a sign of genetic susceptibility to coronary heart disease.