Hereditary hemochromatosis genotypes and risk of ischemic stroke.
OBJECTIVE
We tested the hypothesis that the HFE genotypes H63D/H63D, H63D/wild type, C282Y/H63D, C282Y/C282Y, and C282Y/wild type are risk factors for symptomatic carotid atherosclerosis, ischemic cerebrovascular disease (ICVD), and ischemic stroke.


METHODS
We performed an age- and gender-matched case-control study of 701 cases with symptomatic carotid atherosclerosis vs 2,777 controls, and a prospective study of 9,178 individuals from the Danish general population followed for 24 years, during which 504 developed ICVD, of whom 393 had ischemic stroke.


RESULTS
Genotype was not consistently associated with symptomatic carotid atherosclerosis. The cumulative incidences of ICVD and ischemic stroke by age were increased for H63D/H63D vs wild type/wild type (log-rank: p = 0.003 and p < 0.001). H63D/H63D vs wild type/wild type had an age- and multifactorially adjusted hazard ratio of 2.0 (95% CI: 1.2 to 3.2; p = 0.007) and 2.1 (1.3 to 3.5; p = 0.004) for ICVD and of 2.4 (1.4 to 4.0; p = 0.001) and 2.8 (1.7 to 4.6; p < 0.001) for ischemic stroke; these remained significant after correction for multiple comparisons. Other hereditary hemochromatosis genotypes were not associated with ICVD or ischemic stroke.


CONCLUSIONS
Hereditary hemochromatosis H63D homozygosity predicts a two- to threefold risk of ICVD and ischemic stroke.
Ellervik
C
C
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Tybjaerg-Hansen
A
A
Appleyard
M
M
Sillesen
H
H
Boysen
G
G
Nordestgaard
B G
BG
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000453:epidemiology*; D002340:Carotid Artery Diseases / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*