Mutations in the hemochromatosis gene (HFE) and stroke.
OBJECTIVE
Increased serum iron is found to be a risk factor for stroke. Carriers of HFE C282Y and H63D mutations have elevated serum iron levels and may have an increased risk for stroke. We studied the association between HFE gene mutations, carotid atherosclerosis, and stroke.


METHODS
We compared the frequency of the HFE C282Y and H63D gene mutations in 202 prevalent and incident cases of stroke with that of 2730 controls from a population-based study, the Rotterdam Study. The influence of HFE mutations on the relationship between hypertension, smoking, and stroke was studied by use of a logistic regression model. In the analyses of hypertension, we used noncarriers and nonhypertensives as reference; in the analysis of smoking, we used noncarriers and those who never smoked as the reference group. Furthermore, we studied the mean intima-media thickness of the common carotid artery in relation to hypertension, smoking, and the HFE genotype in subjects without stroke.


RESULTS
The percentage of both C282Y and H63D carriers in cases (43.7%, n=87) did not differ significantly (P=0.09) from that of controls (37.6%, n=986). The odds ratio for stroke for HFE carriers who also suffered from hypertension was 3.0 (95% CI, 1.9 to 4.6), and for HFE carriers who were also smokers, the odds ratio for stroke was 2.6 (95% CI, 1.4 to 5.0). The mean+/-SD intima-media thickness of the carotid artery was 0.77+/-0.14 mm for noncarriers without a history of hypertension or smoking compared with 0.81+/-0.17 mm for HFE carriers who smoked (P<0.004) and 0.84+/-0.20 mm for HFE carriers who were hypertensive (P<0.001).


CONCLUSIONS
Mutations in the HFE gene were not significantly related to stroke or atherosclerosis in the carotid artery. The HFE gene may modify the relationship between smoking and stroke.
D000368:Aged; D001794:Blood Pressure; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006580:Genetic Carrier Screening; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins