Hindorff Lucia A, Psaty Bruce M, Carlson Christopher S, Heckbert Susan R, Lumley Thomas, Smith Nicholas L, Lemaitre Rozenn N, Rieder Mark J, Nickerson Deborah A, Reiner Alexander P
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98101, USA.
Am J Epidemiol. 2006 Apr 1;163(7):600-7. doi: 10.1093/aje/kwj092. Epub 2006 Feb 8.
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. Eight variants representing 98% of common prothrombin variants were selected using publicly available genomic variation data. These variants and the functional G20210A variant were genotyped and used to infer haplotypes in a population-based Washington State case-control study of postmenopausal Caucasian women (1995-1999; 273 cases and 788 controls). Women carrying a nonsynonymous polymorphism in exon 6 (C5467T) had an increased risk of myocardial infarction (for each additional copy, relative to women with one fewer copy, odds ratio = 1.4, 95% confidence interval: 1.0, 1.8). Prothrombin haplotypes were also associated with myocardial infarction (with minimal adjustment, global p = 0.056; with full adjustment, p = 0.034). Associations between haplotypes and myocardial infarction were similar among users of hormone therapy and nonusers (global p = 0.61), though statistical power was limited. These preliminary results suggest that common genetic variants in the prothrombin gene or other variants in linkage disequilibrium are associated with myocardial infarction in postmenopausal women.
凝血因子中的基因变异与心肌梗死相关，并且可能改变激素治疗与心血管疾病风险之间的关联。本研究评估凝血酶原基因的常见变异是否与绝经后女性非致死性心肌梗死的发病有关，以及这种关联是否因当前雌激素使用情况而异。利用公开的基因组变异数据选择了代表98%常见凝血酶原变异的8个变异。在一项基于人群的华盛顿州绝经后白人女性病例对照研究（1995 - 1999年；273例病例和788例对照）中，对这些变异以及功能性G20210A变异进行基因分型，并用于推断单倍型。携带外显子6非同义多态性（C5467T）的女性发生心肌梗死的风险增加（相对于拷贝数少一个的女性，每增加一个拷贝，比值比 = 1.4，95%置信区间：1.0，1.8）。凝血酶原单倍型也与心肌梗死相关（最小调整时，整体p = 0.056；完全调整时，p = 0.034）。在激素治疗使用者和非使用者中，单倍型与心肌梗死之间的关联相似（整体p = 0.61），尽管统计效能有限。这些初步结果表明，凝血酶原基因中的常见基因变异或处于连锁不平衡的其他变异与绝经后女性心肌梗死相关。
