Complement receptor 1 gene polymorphisms are associated with cardiovascular risk

de Vries, Marijke A.; Trompet, Stella; Mooijaart, Simon P.; Smit, Roelof A.J.; Böhringer, Stefan; Castro Cabezas, Manuel; Jukema, J. Wouter

BACKGROUND AND AIMS: Inflammation plays a key role in atherosclerosis. The complement system is involved in atherogenesis, and the complement receptor 1 (CR1) plays a role facilitating the clearance of immune complexes from the circulation. Limited evidence suggests that CR1 may be involved in cardiovascular disease. We investigated the relationship between CR1 gene polymorphisms and cardiovascular risk. METHODS: Single nucleotide polymorphisms (SNPs) within the CR1 region (n = 73) on chromosome 1 were assessed in 5244 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2 years. Logistic regression, adjusted for gender, age, country and use of pravastatin, was used to assess the association between the SNPs and cardiovascular disease. RESULTS: All 73 SNPs within the genomic region of the CR1 gene on chromosome 1 were extracted. In this region, strong LD was present leading to the occurrence of two haploblocks. Twelve of the 73 investigated CR1 SNPs were significantly associated with the risk of fatal or nonfatal myocardial infarction (all p < 0.05). Moreover, most of the associated SNPs were also associated with levels of serum C-reactive protein (CRP). The global p-value for the tail strength method to control for multiple testing was 0.0489, implying that the null hypothesis of no associated SNPs can be rejected. CONCLUSIONS: These data indicate that genetic variation within the CR1 gene is associated with inflammation and the risk of incident coronary artery disease.