on September 28, 2006
Published online before print September 28, 2006, doi: 10.1161/01.ATV.0000247248.76409.8b
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 13, 2006
Accepted on September 13, 2006
Asp92Asn Polymorphism in the Myeloid IgA Fc Receptor Is Associated With Myocardial Infarction in Two Disparate Populations. CARE and WOSCOPS
Olga A. Iakoubova *;
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.), Boston, Mass; and the University of Glasgow and Royal Infirmary (C.J.P., J.S.), Glasgow, UK.
* To whom correspondence should be addressed. 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 (Pinteraction=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 (Pinteraction=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.
Key words: genetic polymorphisms • myocardial infarction • coronary heart disease • inflammation • prevention
This article has been cited by other articles:
 |
|
 |
|
  I. D. Bezemer, A. R. Arellano, C. H. Tong, C. M. Rowland, H. A. Ireland, K. A. Bauer, J. Catanese, P. H. Reitsma, C. J.M. Doggen, J. J. Devlin, et al. F9 Malmo, factor IX and deep vein thrombosis Haematologica, May 1, 2009; 94(5): 693 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Thompson, C. L. Hyde, L. S. Wood, S. A. Paciga, D. A. Hinds, D. R. Cox, G. K. Hovingh, and J. J.P. Kastelein Comprehensive Whole-Genome and Candidate Gene Analysis for Response to Statin Therapy in the Treating to New Targets (TNT) Cohort Circ Cardiovasc Genet, April 1, 2009; 2(2): 173 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Luke, E. S. O'Meara, C. M. Rowland, D. Shiffman, L. A. Bare, A. R. Arellano, W.T. Longstreth Jr, T. Lumley, K. Rice, R. P. Tracy, et al. Gene Variants Associated With Ischemic Stroke: The Cardiovascular Health Study Stroke, February 1, 2009; 40(2): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Qian, F. Xie, A. W. Gibson, J. C. Edberg, R. P. Kimberly, and J. Wu Functional expression of IgA receptor Fc{alpha}RI on human platelets J. Leukoc. Biol., December 1, 2008; 84(6): 1492 - 1500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. van der Net, D. M. Oosterveer, J. Versmissen, J. C. Defesche, M. Yazdanpanah, B. E. Aouizerat, E. W. Steyerberg, M. J. Malloy, C. R. Pullinger, J. J.P. Kastelein, et al. Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia Eur. Heart J., September 2, 2008; 29(18): 2195 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Bezemer, L. A. Bare, C. J. M. Doggen, A. R. Arellano, C. Tong, C. M. Rowland, J. Catanese, B. A. Young, P. H. Reitsma, J. J. Devlin, et al. Gene Variants Associated With Deep Vein Thrombosis JAMA, March 19, 2008; 299(11): 1306 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Iakoubova, C. H. Tong, C. M. Rowland, T. G. Kirchgessner, B. A. Young, A. R. Arellano, D. Shiffman, M. S. Sabatine, H. Campos, C. J. Packard, et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 435 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Shiffman, E. S. O'Meara, L. A. Bare, C. M. Rowland, J. Z. Louie, A. R. Arellano, T. Lumley, K. Rice, O. Iakoubova, M. M. Luke, et al. Association of Gene Variants With Incident Myocardial Infarction in the Cardiovascular Health Study Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 173 - 179. [Abstract] [Full Text] [PDF]
|
|