Nitric Oxide Synthase 2 Polymorphisms (rs2779248T/C and rs1137933C/T) and the Risk of Type 2 Diabetes in Zahedan, Southeastern Iran

Abstract

Background: Nitric oxide (NO) has been associated with insulin resistance and type 2 diabetes (T2D). NO is synthesized enzymatically from l-arginine (l-Arg) by three NO synthase (NOS) isoforms, Neuronal NOS (nNOS or NOS1), Inducible NOS (iNOS or NOS2), and Endothelial NOS (eNOS or NOS3). The impact of NOS2 gene polymorphism was investigated on the susceptibility of T2D in a sample of Iranian population (Southeastern of Iran). Methods: In 2015, the present case-control study was conducted on 152 T2D patients and 157 healthy control subjects (HCs) referring to Bu-ali Hospital of Zahedan, eastern Iran. Genotyping of NOS2 rs2779248T/C and rs1137933C/T variants were done using the Tetra-Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-ARMS PCR) method. Results: CT genotype of rs1137933C/T was significantly associated with increased risk of T2D (P<0.0001). The T allele of this single nucleotide polymorphism (SNP) was also strongly associated with T2D risk (P<0.0001). For rs2779248 T/C, TC genotype of this SNP decreased the risk of T2D (OR=0.25 95%CI= 0.15-0.42, P<0.0001); however, CC genotype of this SNP increased the risk of T2D (P<0.005). There was no significant association between clinical-demographic characteristics of T2D group with respect to both SNPS in dominant. Conclusion: CT genotype and C allele of NOS2 rs1137933 C/T polymorphism were associated with a higher risk of T2D, and no association was observed between T allele of NOS2 rs2779248 T/C polymorphism and T2D while TC genotype of this SNP decreased the risk of T2D in the study participants.

Keywords

• Type 2 diabetes mellitus
• Single nucleotide polymorphism
• Nitric oxide synthase type II
• Inducible nitric oxide synthase