A prospective study of coronary heart disease and the hemochromatosis gene(HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autos omal recessive condition of disordered iron metabolism, absorption, and sto rage. It is possible that people who carry HFE mutations have increased ris k of CHD. We used a prospective case-cohort design (243 CHD cases and 535 n on-cases) to determine whether the HFE C282Y mutation was associated with i ncident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in th e ARIC study population were 0.2% (one homozygous person) and 6%. respectiv ely. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk = 1.60, 95% CI 0.9-2.9). After adjusting for other c onfounding risk factors (age, race, gender. ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, an d triglycerides), the association became stronger (relative risk = 2.70, 95 % CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Ou r prospective findings suggest that individuals carrying the HFE C282Y muta tion may be at increased risk of CHD. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.