POSTER NO: 368

Polymorphic markers of candidate genes and genetic predisposition to ischemic heart disease in Russian patients

¹Olga E. Voron'ko, ²Dmytry A. Zateyshchikov, ¹Natalia M. Gorashko, ²Larissa O. Minushkina, ¹Nadezhda B. Babunova, ²Anna A. Zateyshchikova, ¹Ilya V. Ignatiev, ²Olga Yu. Kudryashova, ²Boris A. Sidorenko, ¹Valery V. Nosikov
¹National Research Centre 'GosNII genetika', Moscow, Russia, ²Russian President's Medical Centre, Moscow, Russia

To study the genetic predisposition to ischemic heart disease (IHD) in Russian patients we have developed a set of polymorphic markers of several candidate genes. We have used Thr174Met and Met235Thr markers of angiotensinogen gene (AGT), I/D and G7831A markers of angiotensin I-converting enzyme gene (ACE), A1166C marker of vascular type 1 angiotensin II receptor gene (AT2R1), Glu298Asp and ecNOS4a/4b markers of endothelial NO synthase gene (NOS3), E2/E3/E4 marker of apolipoprotein E gene (APOE), Lys198Asn marker of endothelin 1 gene (EDN1), and ^677T marker of methylene tetrahydrofolate reductase gene (MTHFR). Two groups of patients have been formed: one group with ischemic heart disease (IHD+, n=172) and IHD- group (n=92) in which all patients had no clinical IHD. We have not found significant association with IHD in case of polymorphic markers of AGT, AT2R1, EDN1, APOE, MTHFR genes and I/D marker of ACE gene. The marker G7831A of ACE gene (another marker designation is PstI +/-) showed a small but statistically insignificant difference in allele and genotype frequencies. The polymorphic markers Glu298Asp and ecNOS4a/4b of NOS3 gene showed significant association with IHD. In the case of Glu298Asp marker of NOS3 gene the carriers of Glu/Glu genotype had lower risk of IHD (OR = 0.60) and the carriers of Glu/Asp genotype had higher risk of IHD (OR = 1.65). The study of allele and genotype distributions of ecNOS4a/4b marker of NOS3 gene has shown that the carriers of 4a allele and 4a/4b genotype had higher risk of IHD (OR = 1.36 and 1.75, correspondingly) whereas the carriers of 4b allele and 4b/4b genotype had lower risk of IHD (OR = 0.74 and 0.56, correspondingly). Conclusions: Our data allow us to suppose that NOS3 gene can be associated with development of IHD among Russian patients in a Moscow population.