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 autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. 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 confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and 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. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.
Division of Epidemiology, School of Public Health, University of Minnesota, Suite 300, 1300 South 2nd Street, Minneapolis, MN 55454-1015, USA.
M L
ML
Rasmussen
A R
AR
Folsom
D J
DJ
Catellier
M Y
MY
Tsai
U
U
Garg
J H
JH
Eckfeldt
D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins