BACKGROUND: Inflammation is important in the pathogenesis of atherosclerosis. Polymorphisms of Fc receptors for IgG (FcgammaR) are associated with modifying effects of several infectious and autoimmune diseases. We have assessed the relationship between polymorphisms in three different FcgammaR genes and coronary artery disease (CAD). METHODS AND RESULTS: We genotyped for the FcgammaRIIA-R/H131, the FcgammaRIIIB-Na1/Na2, and the FcgammaRIIIA-F/V158 polymorphisms in 882 patients undergoing diagnostic coronary angiography. Significant CAD was defined as >/=50% lumen diameter stenosis in at least one coronary artery. In the analysis, no association was found between the FcgammaRIIA and FcgammaRIIIB genotypes and CAD, whereas the FcgammaRIIIA genotype was strongly related. Compared to those being heterozygous, or homozygous for the F allele, patients homozygous for the V allele had significantly reduced risk: OR, 0.53; (CI, 0.32-0.90). Additional adjustment for classical risk factors and sedimentation rate did not affect the results. The V/V genotype was also inversely related to the extent of CAD defined as no CAD, single, double or triple vessel disease (P trend=0.002). CONCLUSIONS: Our data provide evidence for an association between FcgammaRIIIA allelic variants and coronary atherosclerosis. Genetic variation in this IgG-receptor may influence the clearance of antibodies by monocyte-derived macrophages involved in the pathogenesis of CAD.
BACKGROUND:Inflammation is important in the pathogenesis of atherosclerosis. Polymorphisms of Fc receptors for IgG (FcgammaR) are associated with modifying effects of several infectious and autoimmune diseases. We have assessed the relationship between polymorphisms in three different FcgammaR genes and coronary artery disease (CAD). METHODS AND RESULTS: We genotyped for the FcgammaRIIA-R/H131, the FcgammaRIIIB-Na1/Na2, and the FcgammaRIIIA-F/V158 polymorphisms in 882 patients undergoing diagnostic coronary angiography. Significant CAD was defined as >/=50% lumen diameter stenosis in at least one coronary artery. In the analysis, no association was found between the FcgammaRIIA and FcgammaRIIIB genotypes and CAD, whereas the FcgammaRIIIA genotype was strongly related. Compared to those being heterozygous, or homozygous for the F allele, patients homozygous for the V allele had significantly reduced risk: OR, 0.53; (CI, 0.32-0.90). Additional adjustment for classical risk factors and sedimentation rate did not affect the results. The V/V genotype was also inversely related to the extent of CAD defined as no CAD, single, double or triple vessel disease (P trend=0.002). CONCLUSIONS: Our data provide evidence for an association between FcgammaRIIIA allelic variants and coronary atherosclerosis. Genetic variation in this IgG-receptor may influence the clearance of antibodies by monocyte-derived macrophages involved in the pathogenesis of CAD.
Authors: Mahir Karakas; Michael M Hoffmann; Caren Vollmert; Dietrich Rothenbacher; Christa Meisinger; Bernhard Winkelmann; Natalie Khuseyinova; Bernhard O Böhm; Thomas Illig; Winfried März; Wolfgang Koenig Journal: BMC Med Genet Date: 2009-05-29 Impact factor: 2.103