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 > or =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.