Genetic and expression changes in TNF- α as a risk factor for rheumatoid arthritis pathogenesis in northeast India

Abstract

Antitumour necrosis factor-alpha (TNF- α) therapy is used as a clinical intervention for rheumatoid arthritis (RA) but differences exist in response to the treatment which makes the candidature of the screening of TNF- α alteration(s) at genetic and expression levels an important agenda prior to treatment. This study aims to determine the associative role of TNF- α –308G/A polymorphism and differential expression of TNF- α in the pathogenesis of RA. A case–control study where a total of 126 RA patients were enrolled based on ACR-EULAR (2010) criteria, along with 160 community matched age and sex controls over a period of three years. The differential expression level of TNF- α mRNA and protein level was studied and TNF- α –308G/A polymorphism was screened by T-ARMS PCR assay. All statistical analysis was performed using SPSS software. mRNA expression level of TNF- α was upregulated in RA cases (avg. 15.85 ± 9.52 fold) compared to control. TNF- α protein level was found to be higher in RA cases (28.62 ± 7.17 pg/mL) compared to control (23.14 ± 6.91 pg/mL). TNF- α –308 variant GA genotype was higher in RA (46.03%) than in control (25%). The presence of TNF- α –308 variant A allele was associated with increased risk of RA susceptibility (odds ratio (OR) = 2.559 at 95% confidence interval (CI), P< 0.001) but not severity (OR = 1.617 at 95% CI, P= 0.571). The presence of –308 variant genotype was associated with a higher TNF- α mRNA and protein expression. The presence of TNF- α –308A allele is associated with increased risk of RA susceptibility and differential TNF- α expression, and has prognostic significance. Association of higher TNF- α pro-inflammatory cytokine levels with northeast Indian patients makes them suitable subjects for anti-TNF- α therapy.