THE 4A/B POLYMORPHISM OF THE NOS3 GENE AS A PREDICTOR OF SUSCEPTIBILITY AND PROGRESSION OF MULTIPLE SCLEROSIS

Aim. Nitric oxide (NO) and the variants of the endothelial nitric oxide synthase gene (NOS3) in multiple sclerosis (MS) have become a focus of active scientific interest in recent years. The NOS3 gene is constitutively expressed in neuronal and epithelial cells. Moreover, the endothelial NO synthase enzyme (eNOS) activity, which plays a pivotal role in developing endothelial dysfunction, is regulated by variants of the NOS3 gene, including the 4a/b variant. Objective. To evaluate the influence of the 4a/b variant of the NOS3 gene on the susceptibility to and progression of multiple sclerosis. Materials and Methods. The study included 113 patients diagnosed with MS. Genotyping for the 4a/b variant of the NOS3 gene was performed using the polymerase chain reaction method. Results. Our findings indicate that the presence of the 4bb genotype is associated with a reduced risk of developing MS, whereas the 4a allele of the NOS3 gene is linked to an increased risk. Clinical characteristic analysis revealed that patients with the 4ba and 4bb genotypes exhibited a significantly higher body mass index (BMI) (p=0.007) than those with the 4aa genotype. Additionally, patients with the 4bb genotype were substantially more likely to experience a severe disease course (p=0.0489). Binary logistic regression analysis identified a gene-environment interaction between the NOS3 4a/b variant and BMI (p=0.037), suggesting a combined effect of these factors on MS progression. Conclusions. The results underscore the significant and complex role of the NOS3 4a/b variant in the pathogenesis and progression of MS. Further investigation is warranted to deepen our understanding of the mechanisms underlying this genetic factor and its interplay with other contributing variables.