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


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).


CONCLUSIONS
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.
Pai
Jennifer K
JK
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Kresge 9th Floor, Boston, MA 02115, USA. jpai@hsph.harvard.edu
Manson
JoAnn E
JE
Rexrode
Kathryn M
KM
Albert
Christine M
CM
Hunter
David J
DJ
Rimm
Eric B
EB
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017242:Complement Factor H / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
D017242:Complement Factor H