HFE mutations and risk of coronary heart disease in middle-aged women.
BACKGROUND
Although heterozygosity for the C282Y mutation in the HFE gene has been associated with an increased risk of cardiovascular events, epidemiological studies remain inconclusive. The aim of the present study was to obtain further evidence as to whether HFE mutations are associated with risk of coronary heart disease (CHD) in middle-aged women. We used data of a cohort of 15 236 Dutch middle-aged women to investigate whether C282Y carriers and H63D carriers are at increased risk of coronary heart disease compared with non-carriers.


METHODS
Women were included in the study between 1993 and 1997 and were followed until 1 January 2000 for cardiovascular events. HFE genotyping was performed on all 211 coronary heart disease cases and a randomly selected sample from the baseline cohort (n = 1526). A weighted Cox proportional hazards model was used to estimate crude, age-adjusted and multivariate adjusted hazard ratios for C282Y and H63D carriership in relation to coronary heart disease.


RESULTS
Compared with non-carriers, those that carried the C282Y allele were not at increased risk for CHD (HR = 1.25, 95% CI = 0.74-2.09). Neither did we find an association between the H63D mutation and CHD risk (HR = 0.73, 95% CI = 0.43-1.24).


CONCLUSIONS
Our results are in accordance with similar studies to date, for which we present a meta-analysis. HFE mutations appear not to affect the risk of coronary heart disease.
van der A
D L
DL
University Medical Center Utrecht, the Netherlands.
Peeters
P H M
PH
Grobbee
D E
DE
Roest
M
M
Marx
J J M
JJ
Voorbij
H M
HM
van der Schouw
Y T
YT
D000368:Aged; D000483:Alleles; D041322:Chromosomes, Human, Y; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies
D015395:Histocompatibility Antigens Class I