A Relationship between Endothelial Nitric Oxide Synthetase Gene Variants and Substance Use Disorder

Addictive substances are known to result in oxidative stress (OS). OS enhances the generation of free radicals and reactive oxygen species (ROS) and reduces antioxidant capacity. Peroxides and oxygen radicals, including hydrogen peroxide and superoxide and radical nitrogen species, including nitric oxide (NO), are parts of the ROS. Gene variants of the endothelial nitric oxide (eNOS) affect the plasma levels of NO. This study aimed to investigate whether there was an association between eNOS variants and substance use disorders (SUDs) risk in the Turkish population.

Two eNOS variants (G894T and 27 bp VNTR 4b/a in intron 4) were examined in 216 SUD patients and 140 healthy controls. The eNOS variants were assessed with the PCR based on the RFLP analysis. Since the patient group consisted only of men, the control group was examined as a mixed and male-only.

The eNOS G894T homozygous T/T genotype revealed a significant association with susceptibility to SUD. The patients carrying T/T genotype had SUD risk 1.054 times as much as the controls and male controls had (p=0.004 and p=0.038, respectively). eNOS 4a/4a genotype increased in patients as compared to male controls (p=0.048). The homozygous 4b/4b genotype was higher in the male control group than in SUD patients (p=0.029). eNOS VNTR 4a allele was more prevalent in the patients than in both controls and male controls (p=0.026 and p=0.0033, respectively).

This study is one of the first studies investigating the relationship between two eNOS gene variants and SUD in our country. Our findings show that eNOS G894T and VNTR variants may be the significant risk factor for SUDs in Turkish subjects.