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Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women [see comments]
Roest M; van der Schouw YT; de Valk B; Marx JJ; Tempelman MJ; de Groot PG; Sixma JJ; Banga JD
Julius Center for Patient Oriented Research, Utrecht University Medical School, The Netherlands.
Circulation, 100(12):1268-73 1999 Sep 21
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.
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MESH Headings
Aged ; Alleles ; Cardiovascular Diseases *MO ; Cerebrovascular Disorders MO ; Female ; Hemochromatosis *GE ; Heterozygote ; Histocompatibility Antigens Class I *GE HISTOCOMPATIBILITY ANTIGENS CLASS 01 ; Human ; HLA Antigens *GE HLA A ANTIGENS ; Middle Age ; Myocardial Infarction MO ; Polymerase Chain Reaction ; Risk Factors ; Support, Non-U.S. Gov't

Publication Type
Country of Publication
CAS Registry Number
0 (Histocompatibility Antigens Class I); 0 (HLA Antigens); 0 (HLA-H antigen)

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