Association of NOS3-c.894G T transversion with susceptibility to metabolic syndrome in Azar-cohort population: A case-control study and in silico analysis of the SNP molecular effects

Objective(s): We investigated whether NOS3c.894G T transversion (rs1799983), which causes the substitution of glutamate with aspartate (E298D) in the oxygenase domain of endothelial nitric oxide synthase (eNOS), is associated with susceptibility to metabolic syndrome (MetS) risk in IranianAzerbaijanis. Materials and Methods: The frequencies of the alleles and genotypes were compared in the 300 cases and 300 controls using PCRRFLP assay. Also, higherorder MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. In silico analysis was done to introduce a hypothesis describing the molecular effects of NOS3c.894G T. Results: The T allele (OR:1.46; CI:1.0542.04; P=0.02), GT genotype (OR:1.44; CI:1.022.03; P=0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.062.06; P=0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.5333.70; P=0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS3c.894G T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.894G T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, bactin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN. Conclusion: We showed that NOS3c.894G T was associated with an increased risk of MetS in IranianAzerbaijanis, and BMI modulates the effects of NOS3c.894G T genotypes on MetS risk. Also, in silico analysis found that NOS3c.894G T may affect the interaction of the eNOS oxygenase domain with its several functional partners.