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

OBJECTIVES

We investigated whether -c.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 Iranian-Azerbaijanis.

MATERIALS AND METHODS

The frequencies of the alleles and genotypes were compared in the 300 cases and 300 controls using PCR-RFLP assay. Also, higher-order MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. analysis was done to introduce a hypothesis describing the molecular effects of -c.894G>T.

RESULTS

The T allele (OR:1.46; CI:1.054-2.04; =0.02), GT genotype (OR:1.44; CI:1.02-2.03; =0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.06-2.06; =0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.53-33.70; =0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that -c.894G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, investigation revealed that c.894G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, b-actin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN.

CONCLUSION

We showed that -c.894G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of -c.894G>T genotypes on MetS risk. Also, analysis found that -c.894G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners.