CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

Abstract

Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and coronary syndromes. Atherosclerosis is a complex multifactorial disorder. Data indicate that the complement proteins play a crucial role in the link between inflammation and atherogenesis. Thus, there is evidence supporting the role of complement activation in atherogenesis. Complement receptor 1 (CR1) is a membrane protein found on different cells involved in various activities of the complement system. We demonstrated the possible involvement of CR1 in atherosclerosis studying the allele and genotype frequencies of the CR1 Pro1827Arg, CR1 His1208Arg exon 22 and int27 HindIII polymorphisms in a sample of patients with angiographically documented coronary artery disease (CAD) (n=550) and in healthy controls (n=380) matched for age, gender and ethnicity. Our data showed no significant deviations between the two groups with regard to either allele or genotype frequencies. After stratification according to risk factors, our analysis revealed a reduced frequency of the GG genotype of the Pro1827Arg polymorphism in patients with CAD and dyslipidemia vs the controls (p=0.031) and of the GG and LL genotypes in CAD patients with dyslipidemia vs CAD patients without dyslipidemia regarding the Pro1827Arg and CR1 HindIII intron 27 polymorphisms (GG, p=0.019; LL, p=0.184). We analyzed the haplotype frequencies of CR1. A decrease in CAD patients carrying the CAC haplotype compared to controls (p=0.043) and a decrease in the CAC haplotype in CAD patients with hypertension vs healthy controls (p=0.029) were demonstrated. Our data showed a possible involvement of CR1 gene polymorphisms in the predisposition to the development of this disease.