Genetic variation in Fcγ receptor IIa protects against advanced peripheral atherosclerosis

Abstract

SummaryImmune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcγ receptor IIa (FcγRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcγRIIa gene strongly influences binding to FcγRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcγRIIa genotype in 430 subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele were protected against advanced peripheral atherosclerosis (age- and gender-adjusted odds ratio (OR) 0.77 (0.54–1.12) and 0.65 (0.44–0.98), respectively, P trend=0.04). This effect was most pronounced in subjects with modestly elevated levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29–0.93) and 0.45 (0.23–0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcγRIIa protects against advanced peripheral atherosclerosis.