Study of NOS2A Gene Polymorphism in Rheumatoid Arthritis Patients and Normal Individuals

Backhground & Several lines of evidence have indicated that NO might be important in the pathogenesis of RA. NO could be synthesized by an enzyme called inducible nitric oxide synthase (iNOS). iNOS is expressed in the synovium, cartilage and lymphomononuclear cells of synovial fluid and lymphocytes and monocytes of peripheral blood of RA patients. Several studies have shown that iNOS gene (NOS2A) polymorphisms have been associated with a number of inflammatory and autoimmune diseases. In the present study the frequency of NOS2A gene polymorphism at positions -1659 C/T and +150 C/T was investigated in patients with RA and control subjects. In the present case- control study the frequency of NOS2A gene polymorphisms at positions -1659 C/T and +150 C/T was investigated in 176 patients with RA and 232 control subjects using PCR-Allele specific and PCR-RFLP methods, respectively. SPSS version 10,Chi-square and Fisher's exact tests were used to study the differences in genotype and allele frequencies between patients and controls. The results of the present study showed a significant difference in NOS2A -1659 C/T polymorphism between the patients and controls (P=0.03). Wild type homozygote (CC) was significantly higher in normal subjects (75%) than patients (64.2%). No significant difference was observed between RA patients and controls in NOS2A +150 C/T polymorphism (P=0.33). Furthermore, there was no significant association between different clinical and paraclinical findings including erosion, deformity of joints, rheumatoid nodules, extra articular manifestations, CRP, RF and age of onset and -1659 C/T and +150 C/T NOS2A gene polymorphisms. To the best of our knowledge this study was the first research on the NOS2A gene polymorphisms in RA patients. Our results revealing the significant correlation between -1659 C/T genotypes and RA, indicates the importance of iNOS polymorphism in the patients and suggest further studies in other ethnic groups.