Spence Mark S, McGlinchey Paul G, Patterson Chris C, Allen Adrian R, Murphy Gillian, Bayraktutan Ulvi, Fogarty Damian G, Evans Alun E, McKeown Pascal P
Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland, United Kingdom.
Am Heart J. 2004 Nov;148(5):847-51. doi: 10.1016/j.ahj.2004.05.019.
Ischemic heart disease (IHD), the leading cause of death worldwide, is a multifactorial disease arising from the complex interplay of genetic and environmental factors. There is considerable evidence that nitric oxide (NO) plays an important role in protecting against atherosclerosis, the process underlying IHD. Endothelial NO is synthesized from the amino acid l-arginine by the endothelial isoform of NO synthase (eNOS). Thus, polymorphisms of the eNOS gene, by altering production of NO within the vascular endothelium, are potential risk factors for IHD. Several groups have investigated the role of the G894T polymorphism of the eNOS gene in IHD by using case-control association studies; however, its role is unclear because of contradictory results from these studies. We applied family-based association tests to investigate the role of this polymorphism in IHD in a well-defined Irish population.
A total of 1023 individuals from 388 families (discordant sibships and parent-offspring trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for by using the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test.
Both the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test analyses found no statistically significant excess transmission of either allele to affected individuals (P = .57 and P = .38, respectively).
Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the G894T polymorphism of the eNOS gene has a significant role in the development of IHD in our population.
缺血性心脏病（IHD）是全球主要死因，是一种由遗传和环境因素复杂相互作用引起的多因素疾病。有大量证据表明，一氧化氮（NO）在预防动脉粥样硬化（IHD的潜在发病过程）中起重要作用。内皮型一氧化氮由一氧化氮合酶（eNOS）的内皮亚型从氨基酸L-精氨酸合成。因此，eNOS基因多态性通过改变血管内皮中NO的产生，成为IHD的潜在危险因素。几个研究小组通过病例对照关联研究调查了eNOS基因G894T多态性在IHD中的作用；然而，由于这些研究结果相互矛盾，其作用尚不清楚。我们应用基于家系的关联测试来研究该多态性在明确的爱尔兰人群IHD中的作用。
共招募了来自388个家庭（不一致的同胞对和亲子三联体）的1023名个体。通过联合传递不平衡检验/同胞传递不平衡检验和家系不平衡检验来测试该多态性与IHD之间的连锁不平衡。
联合传递不平衡检验/同胞传递不平衡检验和家系不平衡检验分析均未发现任何一个等位基因向患病个体的传递有统计学意义的过量（P值分别为0.57和0.38）。
通过专门为复杂疾病研究设计的可靠的基于家系的关联测试，我们没有发现证据表明eNOS基因的G894T多态性在我们人群的IHD发生中起重要作用。
