OXIDATIVE STRESS MARKERS AND SOD2 Ala16Val POLYMORPHISM AS PREDICTORS OF RHEUMATOID ARTHRITIS ACTIVITY IN AN UZBEK POPULATION OF THE FERGANA VALLEY

Parpiyeva S.B.; Aleynik V.A.; Vasilevskiy E.A.; Dadabaev O.T.

Authors

Parpiyeva S.B. Department of Internal Medicine, Andijan State Medical Institute, Andijan, Republic of Uzbekistan
Aleynik V.A. Department of Normal and Pathological Physiology, Andijan State Medical Institute
Vasilevskiy E.A. Department of General Surgery and Transplantology, Andijan State Medical Institute.
Dadabaev O.T. Department of General Surgery and Transplantology, Andijan State Medical Institute.

Keywords:

Rheumatoid arthritis, oxidative stress, malondialdehyde, procalcitonin, SOD2 polymorphism, Ala16Val, mitochondrial dysfunction, Uzbek population.

Abstract

Background: to investigate the role of oxidative stress markers (malondialdehyde, MDA; procalcitonin, PCT) and SOD2 Ala16Val polymorphism (rs4880) in rheumatoid arthritis (RA) pathogenesis and to establish their associations with disease activity in an Uzbek population. Methods: 100 patients with verified RA based on ACR/EULAR 2010 criteria and 73 ethnically-matched healthy controls were enrolled. MDA levels were measured by colorimetric thiobarbituric acid reactive substances (TBARS) assay; PCT was determined by chemiluminescent immunoassay. SOD2 Ala16Val genotyping was performed by real-time PCR with TaqMan probes. Associations between markers, genotypes and disease activity (DAS28-ESR) were analyzed using Spearman correlation, ROC analysis and logistic regression. Results: MDA levels showed dose-dependent activation across RA activity subgroups (3.42±0.21 to 7.86±0.42 μmol/L, p<0.001) and exhibited strong correlation with DAS28-ESR (ρ=0.69; p<0.001). PCT increased from 0.082±0.008 to 0.284±0.019 ng/mL across activity subgroups with strong intercorrelation with MDA (ρ=0.71; p<0.001). The T allele of SOD2 Ala16Val was associated with increased RA risk (OR=1.65; 95% CI: 1.07–2.52; AUC=0.62) and showed significant correlation with MDA levels (ρ=0.58; p<0.001). MDA levels were progressively higher in carriers of the unfavorable Val allele (CC: 4.21±0.32; CT: 5.48±0.28; TT: 7.84±0.42 μmol/L; p<0.001). Conclusions: MDA and PCT serve as integrated biomarkers of systemic inflammation and oxidative stress in RA patients of an Uzbek population. The SOD2 Ala16Val polymorphism is independently associated with RA risk and with elevated MDA levels, providing a mechanistic link between mitochondrial antioxidant capacity and disease severity. The threshold MDA value of 5.5 μmol/L is recommended as a marker of pronounced oxidative stress associated with aggressive RA course.