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

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.

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.

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).

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.