Endothelial nitric oxide synthase gene polymorphism and ischemic heart disease

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.