title: Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women.
abstract: Background-The genetic background of hereditary hemochromatosis (HH) is homozygosity for a cysteine-to-tyrosine transition at position 282 in the HFE gene. Heterozygosity for HH is associated with moderately increased iron levels and could be a risk factor for cardiovascular death. Methods and Results-We studied the relation between HH heterozygosity and cardiovascular death in a cohort study among 12 239 women 51 to 69 years of age residing in Utrecht, the Netherlands. Women were followed for 16 to 18 years (182 976 follow-up years). The allele prevalence of the HH gene in the reference group was 4.0 (95% CI 2.9 to 5.4). The mortality rate ratios for HH heterozygotes compared with wild types was 1.5 (95% CI 0.9 to 2.5) for myocardial infarction (n=242), 2.4 (95% CI 1.3 to 3. 5) for cerebrovascular disease (n=118), and 1.6 (95% CI 1.1 to 2.4) for total cardiovascular disease (n=530). The population-attributable risks of HH heterozygosity for myocardial infarction and cerebrovascular and total cardiovascular death were 3. 3%, 8.8%, and 4.0%, respectively. In addition, we found evidence for effect modification by hypertension and smoking. Conclusions-We found important evidence that inherited variation in iron metabolism is involved in cardiovascular death in postmenopausal women, especially in women already carrying classic risk factors.
authors.affiliation: Julius Center for Patient Oriented Research, Utrecht University Medical School, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Roest
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: B
authors.initials: B
authors.lastname: de Valk
authors.forename: J J
authors.initials: JJ
authors.lastname: Marx
authors.forename: M J
authors.initials: MJ
authors.lastname: Tempelman
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: J D
authors.initials: JD
authors.lastname: Banga
mesh_terms: D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000401:mortality*; D002561:Cerebrovascular Disorders / Q000401:mortality; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D016133:Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins