Genetic variation in Fcgamma receptor IIa protects against advanced peripheral atherosclerosis. The Rotterdam Study.
Immune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcgamma receptor IIa (FcgammaRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcgammaRIIa gene strongly influences binding to FcgammaRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcgammaRIIa 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 FcgammaRIIa protects against advanced peripheral atherosclerosis.
van der Meer
Irene M
IM
Erasmus Medical Center, Department of Epidemiology and Biostatistics, 3000 DR Rotterdam, The Netherlands.
Witteman
Jacqueline C M
JC
Hofman
Albert
A
Kluft
Cornelis
C
de Maat
Moniek P M
MP
D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics*; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000737:chemistry* / Q000235:genetics*; D012306:Risk
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D017452:Receptors, IgG