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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2763.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Asp92Asn Polymorphism in the Myeloid IgA Fc Receptor Is Associated With Myocardial Infarction in Two Disparate Populations

CARE and WOSCOPS

Olga A. Iakoubova; Carmen H. Tong; Anand P. Chokkalingam; Charles M. Rowland; Todd G. Kirchgessner; Judy Z. Louie; Lynn M. Ploughman; Marc S. Sabatine; Hannia Campos; Joseph J. Catanese; Diane U. Leong; Bradford A. Young; David Lew; Zenta Tsuchihashi; May M. Luke; Christopher J. Packard; Kim E. Zerba; Peter M. Shaw; James Shepherd; James J. Devlin; Frank M. Sacks

From Celera Inc (O.A.I., C.H.T., A.P.C., C.M.R., J.Z.L., J.J.C., D.U.L., B.A.Y., D.L., M.M.L., J.J.D.), Alameda, Calif; Pharmaceutical Research Institute (T.G.K., L.M.P., Z.T., K.E.Z., P.M.S.), Bristol-Myers Squibb, Princeton, NJ; Brigham & Women’s Hospital (M.S.S., F.M.S.), Harvard Medical School, Boston, Mass; Harvard School of Public Health (H.C., F.M.S.), Boston, Mass; the University of Berkeley (A.P.C.), Calif; and the University of Glasgow and Royal Infirmary (C.J.P., J.S.), Glasgow, UK.

Correspondence to Iakoubova, MD, PhD, Celera Inc, 1401 Harbor Bay Parkway, Alameda, CA 94502. E-mail olga.iakoubova{at}celeradiagnostics.com

Objective— Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin.

Methods and Results— In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P_interaction=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P_interaction=0.55).

Conclusions— Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.

In CARE, the FCAR 92Asn allele predicted MI (HR=1.68). Pravastatin significantly reduced the risk of MI in carriers of the 92Asn risk allele but not in noncarriers. In WOSCOPS, the 92Asn allele was associated with CHD (OR=1.46), and pravastatin reduced odds of CHD in both carriers and noncarriers.

Key Words: genetic polymorphisms • myocardial infarction • coronary heart disease • inflammation • prevention

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