Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction.
نویسندگان
چکیده
We hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction =.03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy.
منابع مشابه
Common genetic variation in the prothrombin gene, hormone therapy, and incident nonfatal myocardial infarction in postmenopausal women.
Genetic variants in coagulation factors are associated with myocardial infarction and may modify the association between hormone therapy and cardiovascular disease risk. This study assessed whether common variation in the prothrombin gene was associated with incident nonfatal myocardial infarction in postmenopausal women and whether this association differed according to current estrogen use. E...
متن کاملGenetic variants of coagulation factor XIII and the risk of myocardial infarction in young women.
متن کامل
Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women.
CONTEXT Estrogens are known to be prothrombotic, and findings from the Heart and Estrogen/progestin Replacement Study suggest that in women with clinically recognized heart disease, hormone replacement therapy (HRT) may be associated with early harm and late benefit in terms of coronary events. OBJECTIVE To assess whether, as hypothesized, prothrombotic mutations modify the association betwee...
متن کاملPolymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women.
BACKGROUND AND PURPOSE Although family studies have suggested a genetic influence on hemorrhagic stroke, the underlying genetic risk factors remain poorly defined. Coagulation factor XIII, which is involved in hemostasis, fibrinolysis, vascular remodeling, and tissue repair, represents a candidate gene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding-sequ...
متن کاملمقایسه اثـر دو رژیـم هورمـون درمانی در زنان منـوپوز بر لیپیدها و فعالیت فاکتورهای انعقادی فیبرینـوژن، VII، VIII و IX
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ورودعنوان ژورنال:
- Blood
دوره 102 1 شماره
صفحات -
تاریخ انتشار 2003