FcgammaRIIa 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 Fcgamma receptor IIa (FcgammaRIIa), the main receptor for CRP, are involved in CRP-related cardiovascular risk. We evaluated the potential impact of FcgammaRIIa through a genetic association study in patients with ACS.


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 FcgammaRIIa, 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=1.2x10(-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 FcgammaRIIa 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 FcgammaRIIa variant could help to improve risk stratification in the course of coronary disease in the future.
Raaz
Dorette
D
Department of Cardiology and Angiology, University Hospital Erlangen, Germany. Dorette.Raaz@uk-erlangen.de
Herrmann
Martin
M
Ekici
Arif B
AB
Klinghammer
Lutz
L
Lausen
Berthold
B
Voll
Reinhard E
RE
Leusen
Jeanette H W
JH
van de Winkel
Jan G J
JG
Daniel
Werner G
WG
Reis
André
A
Garlichs
Christoph D
CD
D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012306:Risk
C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D002097:C-Reactive Protein