The association between a common FCGR2A polymorphism and C-reactive protein and coronary artery disease revisited.

Introduction: the FcγRIIa receptor is responsible for the clearance of large immune complexes and recently has been proved to be a C-reactive protein (CRP) receptor as well. A polymorphism in the corresponding FCG2RA gene resulting in an amino acid change (R131H) has been implicated, with conflicting results in the pathogenesis of various autoimmune or inflammatory disorders (e.g., atherosclerosis and coronary artery disease [CAD]).

Methods: we recently developed a real-time polymerase chain reaction and melting curve analysis method for the genotyping of the above polymorphism. We further looked at its validity with bioinformatics study and DNA sequencing. Then we genotyped 134 CAD patients and 45 angiographically normal controls and determined serum high-sensitivity CRP by nephelometry (Dade-Behring). Also, we used apparently healthy platelet donors (n = 206) as a larger control group.

Results: our method is accurate and devoid of problems with homologs and copy number variants. The need for reference materials is stressed. There were statistically significant differences (p < 0.05) between the CAD patients and each of the two other control groups, with the percentage of RR genotype rising from 6.5% and 11% in the control groups to an average of 19% in all CAD patients (17%, 24%, and 18.5% in stable angina, unstable angina, and myocardial infarction, respectively). In a logistic regression model that included known risk factors for CAD including CRP, the RR genotype remained a significant predictor for CAD (odds ratio: 6.3 [1.1-36.3]). Also after linear regression analysis, CRP levels were reduced in the RR carriers (vs. HH + HR), controlling for age, sex, and disease (marginal p = 0.07).

Conclusions: with our accurate genotyping method, the RR genotype was correlated with atherothrombotic CAD events. The inverse correlation found between CRP levels and genotype supports the in vitro data of RR cells binding CRP stronger than HH.