?717A>G polymorphism of human C-reactive protein gene associated with coronary heart disease in ethnic Han Chinese: the Beijing atherosclerosis study

Abstract

Serum C-reactive protein (CRP) has been strongly implicated in the pathogenesis of coronary heart disease (CHD). We report here on the association between gene coding for CRP and CHD in the ethnic Han population of China. For this purpose two polymorphisms of -717A>G and +2147A>G of the CRP gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients and these were further investigated for associations with CHD in 619 male patients and 615 age-matched male normal controls. The frequency of A allele carriers of -717A>G polymorphism was significantly higher in patients than in controls by univariate analysis. After controlling for other risk factors the association between this polymorphism and CHD remained significant by multivariate logistic regression analysis. Individuals carrying the -717A allele had an approx. 6.8-fold higher risk of developing CHD (odds ratio 6.84 compared with those not carrying this allele). Haplotype analysis confirmed the results of individual polymorphism analyses. However, the resolution of effect size is poor, which may be due to the deficiency in sample size of this study. Neither polymorphism was observed to have an influence on serum CRP level. Since the frequency difference between CHD cases and controls for the -717A allele carriers is only 2.28%, and homozygosity for -717G occurs in only 1.78% of subjects, -717 A>G polymorphism is not a major determinant of population genetic risk of CHD in the Chinese population. The association of this polymorphism with CHD supports the belief that carriers of -717A allele of the CRP gene are genetically predisposed to CHD in the Chinese Han population, and it remains possible that this polymorphism is in disequilibrium with one as yet unidentified functional polymorphism in the vicinity.