Investigation of the association between nitric oxide synthase gene variants and NAFLD in adolescents with obesity.

Objectives: The present study aimed to investigate whether nitric oxide synthase (NOS) enzyme gene variants (iNOS rs1060826, eNOS rs1799983, eNOS 27-bp VNTR) play a role in the etiopathogenesis of nonalcoholic fatty liver (NAFLD) in adolescents.

Methods: This cross-sectional study was conducted with obese adolescents [body mass index (BMI) standard deviation score (SDS) ≥2] aged 10-19 years (104 individuals) and age- and sex-matched healthy individuals (64 individuals) whose presence of NAFLD was determined by ultrasound. The iNOS rs1060826 and eNOS rs1799983 variants were performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method, and the eNOS 27-bp VNTR variant was analyzed using the PCR method. The genotypes detected were compared between the patient group and the healthy controls and with the clinical parameters of the patients.

Results: iNOS rs1060826 and eNOS rs1799983 were independent of obesity, whereas eNOS 27-bp VNTR was independent of NAFLD. However, in the obese group, especially in those with NAFLD (+), the iNOS rs1060826 GG genotype was found to be associated with lower diastolic blood pressure (DBP) (p=0.011). Compared with the clinical parameters, insulin resistance (HOMA-IR) was higher in those carrying the eNOS rs1799983 gene variant-TT genotype in the NAFLD (+) group (p=0.051).

Conclusions: While the three functional gene variants of the NOS enzyme did not show a significant difference in terms of genotype between patients and healthy controls, it was determined that both the iNOS rs1060826 gene variant-GG allele was associated with low DBP and HOMA-IR may be higher in those carrying the eNOS rs1799983 gene variant TT genotype in NAFLD (+) patients. The iNOS rs1060826 polymorphism is a potentially important genetic variant that may influence DBP regulation through its effects on nitric oxide production.