Background Recently endothelial nitric oxide synthase (eNOS) T-786C gene promoter polymorphism was considered to be a factor of a high severity of RA [1,2]. It is possible that the eNOS T-786C gene promoter polymorphism can modify the efficacy and safety of treatment in patients with RA, but there is no information on the subject.
Objectives To evaluate efficacy of treatment of patients with RA in accordance to the eNOS T-786C gene promoter polymorphism.
Methods Patients who were enrolled in the study satisfied follows criteria: MTX 10–15 mg/week during the past 12 weeks, stable oral NSAIDs and corticosteroids (CCS), ≤10 mg/day prednisone or equivalent during the past 2 weeks, DAS28 ≥3.2, >6 tender and swollen joints. We excluded patients with previous biologic agent treatment history. All patients received treatment that included MTX, folic acid, CCS, NSAIDs. We evaluated RA activity (DAS28), number of swollen and tender joints, ESR, CRP, and HAQ before enrollment in the study and at the 12 week. Efficacy of the treatment was assessed by the ACR 20; 50; 70 at the end of the study.
The 12-week study completed 148 patients with RA, 100% female, aged 45.7±8.54 years (mean ± SD), with moderate (DAS28 3.2–5.1; 34.5%) and high disease activity (DAS28 >5.1; 65.5%). Among the patients with RA, seropositive were 81.8% and 84.5% by the RF and the anti-CCP, respectively. Polymorphism of NOS3 T786C gene (rs2070744) was performed by Real-Time PCR. All studied polymorphism satisfied Hardy-Weinberg equilibrium. The study was conducted in accordance with the Declaration of Helsinki of the World Medical Association “Ethical principles of medical research involving human subjects” (2000), the requirements of GCP, the applicable national legislation.
Results Among patients with RA frequency of the genotypes was as follows: TT – 37.2%, TC – 42.6%, CC – 20.3%. Age, seropositivity and the duration of the disease were not differing in patients with RA, carriers of the different genotypes of eNOS. Though, CC genotype was associated with high disease activity according to DAS28-ESR >5.2 (OR=9.60; 95% CI 2.18–42.2), HAQ >2 (OR =2.38; 95% CI: 0.94–6.02) and extraarticular manifestations (OR =3.26; 95% CI 1.40–7.56).
After 12 weeks treatment we estimated, that among patients with TT genotype there were 58.3; 16.7; and 8.3% responders ACR20; ACR50; ACR70, and among patients with CC genotype - 20.0; 10.0; 0.0% (p<0.05). TC heterozygotes patients had lower (by 22–25%, p<0.05) clinical response to the treatment by DAS28 and HAQ than the homozygotes TT.
Conclusions eNOS T-786C gene promoter polymorphism influence on the efficacy of the treatment, and CC genotype can be considered as a possible predictor of a low response to the treatment in patients with rheumatoid arthritis.
Breedveld F.C., Weisman M.H., Kavanaugh A.F. et al. (2006) The PREMIER study. Arthr. Reum., 54: 26–37.
Gonzalez-Gay M.A., Llorca J., Palomino-Morales R. et al. (2009) Influence of nitric oxide synthase gene polymorphisms on the risk of cardiovascular events in rheumatoid arthritis. Clin. Exp. Rheumatol., 27 (1): 116–119.
Disclosure of Interest None declared