Butt Christopher, Zheng Hong, Randell Edward, Robb Desmond, Parfrey Patrick, Xie Ya-Gang
Discipline of Laboratory Medicine, Memorial University of Newfoundland, St John's, NF, Canada.
Blood. 2003 Apr 15;101(8):3037-41. doi: 10.1182/blood-2002-09-2888. Epub 2002 Dec 12.
Studies associating the prothrombin 20210G>A (FII 20210A), factor V Leiden (FVL), and factor XIII Leu34 (FXIII-A Leu34) alleles with myocardial infarction (MI) have yielded conflicting results. Complicated gene-gene interactions, small sample sizes, and heterogeneous genetic and environmental backgrounds may contribute to opposing findings. Simultaneous analysis of multiple gene variants in a large sample size from a genetically isolated population may overcome these weaknesses. Genotyping was performed in 500 MI patients and 500 control subjects from the genetically isolated Newfoundland population to determine the prevalence of the FII 20210A, FVL, and FXIII-A Leu34 variants and their association with MI. Gene-gene interactions were also analyzed. The prevalence of the FII 20210A allele was higher in MI patients (3.2%) than in control subjects (1.0%; P =.015). The FII 20210A allele was also 5.6-fold higher in MI patients younger than 51 years than in age-matched control subjects (P =.04). FVL showed 3.9-fold higher prevalence in young patients than in patients older than 50 years (P =.004) and 2.7-fold higher than in age-matched control subjects (P =.007). Furthermore, the prevalence of combined carriers of the FXIII-A L34 and FII 20210A alleles was 12-fold higher in MI patients than in control subjects (P =.002) and with 92% penetrance. There was disequilibrium of the FXIII-A Leu34 allele to MI patients carrying the FII 20210A allele as a genetic background. Based on our data, we determined that (1) the FII 20210A allele is a risk factor for MI, possibly important for early onset; (2) FVL may predispose for early-onset MI; (3) the FXIII-A Leu34 allele predisposes for MI in males only; however, (4) interaction between the FII 20210A and FXIII-A Leu34 alleles forms a synergistic coeffect that strongly predisposes for MI, placing combined carriers at high risk for MI.
将凝血酶原20210G>A（FII 20210A）、因子V莱顿突变（FVL）和因子XIII亮氨酸34（FXIII-A Leu34）等位基因与心肌梗死（MI）相关联的研究得出了相互矛盾的结果。复杂的基因-基因相互作用、小样本量以及异质性的遗传和环境背景可能导致了相反的研究结果。对来自遗传隔离人群的大样本进行多个基因变异的同时分析可能会克服这些弱点。对来自遗传隔离的纽芬兰人群的500例MI患者和500例对照受试者进行基因分型，以确定FII 20210A、FVL和FXIII-A Leu34变异的患病率及其与MI的关联。还分析了基因-基因相互作用。FII 20210A等位基因在MI患者中的患病率（3.2%）高于对照受试者（1.0%；P = 0.015）。在年龄小于51岁的MI患者中，FII 20210A等位基因也比年龄匹配的对照受试者高5.6倍（P = 0.04）。FVL在年轻患者中的患病率比年龄大于50岁的患者高3.9倍（P = 0.004），比年龄匹配的对照受试者高2.7倍（P = 0.007）。此外，FXIII-A L34和FII 20210A等位基因的联合携带者在MI患者中的患病率比对照受试者高12倍（P = 0.002），外显率为92%。以携带FII 20210A等位基因为遗传背景的MI患者中，FXIII-A Leu34等位基因存在失衡。根据我们的数据，我们确定：（1）FII 20210A等位基因是MI的一个危险因素，可能对早发很重要；（2）FVL可能易患早发性MI；（3）FXIII-A Leu34等位基因仅使男性易患MI；然而，（4）FII 20210A和FXIII-A Leu34等位基因之间的相互作用形成了一种协同效应，强烈地使个体易患MI，使联合携带者处于MI的高风险中。
