Polymorphic markers at the genes encoding the endothelial NO-synthase and angiotensin II type 1 receptor and the susceptibility to ischemic heart disease

Allele and genotype frequency distribution patterns of the polymorphic regions at the genes for human endothelial NO-synthase (NOS3) (the ecNOS4a/4b VNTR and the Glu298Asp substitution) and the angiotensin II. type I receptor (AT(1))(the A1166C substitution) were compared in 83 unrelated healthy individuals and 88 patients with ischemic heart disease (IHD). In the group of patients statistically significantly higher frequencies of the NOS3 allele 4a (45.5 versus 19.3%), as well as the 4a/4a (15.9 versus 2.4%) and 4a/4b (59.1 versus 33.7%) genotypes were observed. Frequencies of the allele 4b (54.5% versus 80.7%) and the 4b/4b homozygotes (25.0 versus 63.9%) were statistically significantly lower in the group of IHD patients than in healthy individuals. The IHD patients were statistically significantly different from the healthy subjects also in the distributions of the AT(1) genotypes. In the former group, a significantly decreased frequency of the AA homozygotes (51.1 versus 65.1%) and an increased frequency of AC heterozygotes (40.9 versus 27.7%) were observed. Thus, in the Moscow population the ecNOS4a/4b VNTR of the NOS3 gene and the A1166C polymorphism of the AT(1) gene are associated with the IHD development. Furthermore, the correlation with the IHD revealed was much stronger for the NO3 VNTR locus.