Association of NOS3 Genetic Polymorphism With the Predisposition to Diabetes and Pre-Diabetes, Retrospective Study

Abstract Background: Endothelial nitric oxide synthetase (eNOS) encoded by NOS3 gene has an important role in modulating vascular endothelial function. Many studies reported a possible role of NOS3 in the pathogenesis of diabetes mellitus (DM). This study investigated the association of NOS3 (G>T) rs1799983 genetic polymorphism with DM, pre-diabetes (pre-DM), and insulin resistance (IR). Methods: A random sample of 220 subjects (DM & pre-DM) compared with 220 healthy subjects. Sample obtained from Palestinian adults who consented to genetic and biochemical testing. All subjects genotyped for NOS3 (G > T) rs1799983 SNP using ARMS PCR. Fasting blood sugar (FBS) and triglyceride (TGA) levels were obtained for all subjects. Triglyceride glucose index (TyG) was used as a surrogate marker for IR. Regression analysis adjusted for age and body mass index (BMI) was performed to investigate the association between DM & Pre-DM status, FBS, and TyG with NOS3 genetic polymorphism. Results: NOS3 minor allele frequency positively correlated with FBS levels after controlling for age and BMI (P-value 0.006). DM & pre-DM were more frequent in homozygous NOS3 subjects with an odds ratio of 2.04 (P = 0.05). NOS3 minor allele frequency positively correlated with TyG but not statistically significant association (P = 0.061). Discussion: Many studies reported a potential role of NOS3 genetic polymorphism in DM and IR pathogenesis. In this study, NOS3 minor allele frequency positivity correlated with FBS levels. Homozygous NOS3 was associated with a 2-fold increase in the prevalence of DM & pre-DM. NOS3 genetic polymorphism didn’t show a statistically significant correlation with TyG (P = 0.061). With the increasing availability of genetic testing, NOS3 may serve as an early screening tool to identify subjects with a high risk for elevated FBS. Further studies are required to understand the exact role of NOS3 genetic polymorphism in the pathogenesis of DM, and to evaluate the clinical efficacy and cost-effectiveness of genetic testing. Conclusion: NOS3 genetic polymorphism has a statistically significant relationship with the FBS level. Further studies are required to confirm the association between NOS3 and DM.