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European Heart Journal Advance Access originally published online on May 4, 2007
European Heart Journal 2007 28(11):1297-1303; doi:10.1093/eurheartj/ehm090
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Complement factor H (Y402H) polymorphism and risk of coronary heart disease in US men and women

Jennifer K. Pai1,*, JoAnn E. Manson1,2,3, Kathryn M. Rexrode2,3, Christine M. Albert2,4, David J. Hunter1,3 and Eric B. Rimm1,3

1 Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Kresge 9th Floor, Boston, MA 02115, USA
2 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
4 Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Received 16 October 2006; revised 5 March 2007; accepted 15 March 2007; online publish-ahead-of-print 4 May 2007.

* Corresponding author. Tel: +1 617 432 7722; fax: +1 617 432 2435. E-mail address: jpai{at}hsph.harvard.edu

Aims: Complement factor H (CFH) Y402H polymorphism is located in a region that binds C-reactive protein and may affect inflammatory processes and risk of coronary heart disease (CHD). We assessed the association between Y402H and risk of CHD in nested case–control studies among two large prospective cohorts of US male health professionals and female nurses.

Methods and results: Among participants who were disease-free at baseline, we confirmed 266 (men) and 249 (women) incident CHD deaths and non-fatal myocardial infarctions (MIs) over 6 and 8 years of follow-up, respectively. Using risk-set sampling, controls were matched 2:1 on the basis of age, smoking, and date of blood draw. Comparing homozygous HH with YY, the relative risk (RR) of CHD was 0.94 [95% confidence interval (CI) 0.59–1.49] among men and 0.51 (95% CI 0.29–0.89) among women (pooled RR 0.73, 95% CI 0.51–1.04). The HH genotype was inversely associated with CHD among those <65 years at onset (men: RR 0.39, 95% CI 0.16–0.95; women: 0.21, 95% CI 0.07–0.65; pooled: 0.30, 95% CI 0.15–0.61), but not among those ≥65 years (pooled RR 1.09, 95% CI 0.71–1.68).

Conclusion: CFH Y402H was inversely associated with CHD among women, but not men. This inverse association was observed in both populations with earlier age of CHD.

Key Words: Inflammation • Coronary heart disease • Genetics • Epidemiology • Complement factor H


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