Genetic variation in Fcγ receptor IIa protects against advanced peripheral atherosclerosis The Rotterdam Study
Irene M. van der Meer (1), Jacqueline C. M.Witteman (1),Albert Hofman (1), Cornelis Kluft (2), Moniek P. M. de Maat (2)
(1) Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam,The Netherlands (2) Gaubius Laboratory, TNO-Prevention and Health, Leiden, The Netherlands
Immune processes play a substantial role in atherosclerotic
disease. The role in atherosclerosis of Fcγ receptor IIa (Fc?RIIa),
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
Fc?RIIa 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 Fc?RIIa
protects against advanced peripheral atherosclerosis.