FcγRIIa genotype is associated with acute coronary syndromes as first manifestation of coronary artery disease

Abstract

Objective Identification of clinically relevant determinants for acute coronary syndromes (ACS) promises reduction of ACS-associated mortality. C-reactive protein (CRP) has proved to be useful identifying people at risk for cardiovascular events. However, it is unknown whether genetic variants at Fcγ receptor IIa (FcγRIIa), the main receptor for CRP, are involved in CRP-related cardiovascular risk. We evaluated the potential impact of FcγRIIa through a genetic association study in patients with ACS. Methods and results We conducted a genetic association study among 701 consecutive patients with first event of ACS compared to 467 patients with stable angina pectoris. All patients were genotyped for a frequent functional variant at position 131 of the mature FcγRIIa, where the arginine (R) allele results in an increased signal transduction upon CRP binding. In our study, the R/R131 genotype was significantly associated with ACS as the first manifestation of coronary artery disease ( P = 1.2 × 10 −9, odds ratio 2.86, 95% CI: 2.06–3.99) compared to the non-R/R131 genotype. Conclusions Our data show a genetic association of the FcγRIIa R/R131 genotype with a more frequent occurrence of ACS as the first manifestation of coronary artery disease, probably mediated via its interaction with CRP. Genotyping of this FcγRIIa variant could help to improve risk stratification in the course of coronary disease in the future.