Association of NOS3 and TNF Genetic Polymorphisms With the Predisposition to Elevated Cholesterol, Retrospective Study

Abstract Background: Endothelial nitric oxide synthetase (eNOS) encoded by NOS3 gene has an important role in modulating vascular endothelial function. TNFα gene is responsible for coding TNFα protein that plays a significant role in regulating body inflammation and lipid metabolism. Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated total cholesterol (TC) level, low-density lipoprotein (LDL), triglyceride (TG). In this study, we investigated the association of NOS3 (G>T) rs1799983 and TNFα -308G>A rs1800629 genetic polymorphisms with TC level. Methods: A random sample of 250 subjects with an elevated TC level (defined by TC level ≥ 200mg/dL) compared with 500 healthy subjects. Sample obtained from Palestinian adults who consented to genetic and biochemical testing. Subjects genotyped for NOS3 SNP (G > T) rs1799983 and TNFα -308G>A rs1800629 using ARMS PCR. TC level was obtained for all subjects. Logistic regression analysis adjusted for age and body mass index (BMI) was performed to test for association between NOS3 and TNFα genetic polymorphisms and TC level. Results: NOS3 T allele was significantly more frequent in the elevated TC group, (odds ratio = 1.8, 95% CI =1.02–3.18) with likelihood ratio statistically significant (P = 0.004). Homozygous TNFα variant was more frequent in the elevated cholesterol group without a statistically significant association (P = 0.54). Discussion: Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated TC levels. Homozygous NOS3 variant was associated with a 1.8-fold increase in the risk of high TC after adjustment for age and BMI. TNFα polymorphism didn’t show a statistically significant association with having elevated TC levels. With the increasing popularity and availability of genetic testing, NOS3 can serve as a screening tool to identify people with high risk for elevated TC. Further studies are required to understand the exact role of NOS3 genetic polymorphism in cholesterol metabolism. Conclusion: NOS3 genetic polymorphism had a statistically significant relationship with TC levels. These results support the association between NOS3 polymorphism and elevated TC.