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

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 Fc gamma receptor IIa (Fc gamma RIIa), the main receptor for CRP, are involved in CRP-related cardiovascular risk. We evaluated the potential impact of Fc gamma RIIa 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 Fc gamma RIIa, 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 x 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 Fc gamma RIIa 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 Fc gamma RIIa variant could help to improve risk stratification in the course of coronary disease in the future. (c) 2009 Elsevier Ireland Ltd. All rights reserved.