Tumour Necrosis Factor α Gene Polymorphism in Rheumatoid Arthritis and its Association with Oxidative Stress and Dyslipidemia

Abstract

Introduction: Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects joints. Increased oxidative stress and inflammation due to elevated levels of Tumour Necrosis Factor-α (TNF-α) leads to pathogenesis of RA. Single Nucleotide Polymorphisms (SNPs) in the promoter region of the TNF gene affects the expression of this pro-inflammatory cytokine TNF-α and TNF-α often leads to development of dyslipidaemia in RA cases. Aim: To investigate the association of SNP, TNFα-308G/A with disease development, plasma TNF-α levels, disease biomarkers, oxidative stress and dyslipidaemia parameters in RA cases. Materials and Methods: In this analytical case-control study, hundred cases of RA diagnosed according to American College of Rheumatology (ACR) Criteria 2010, were recruited from Outpatient Department at Guru Teg Bahadur Hospital, Delhi. Age and sex-matched, 100 apparently healthy individuals were recruited as controls. TNF-α-308G/A polymorphism in cases and controls were screened by Polymerase Chain ReactionRestriction Fragment Length Polymorphism (PCR-RFLP). Plasma TNF-α, anti-Cyclic Citrullinated Peptide antibody (anti-CCP), Rheumatoid Factor (RF), and C-Reactive Protein (CRP) were quantified by Enzyme-Linked Immuno Sorbet Assay (ELISA). Biochemical and oxidative stress parameters were measured by standard reference methods. Simple binary logistic regression analysis was done to determine the genetic association of disease with TNF-α-308G/A polymorphism. ANOVA was used for comparative analysis and Pearson’s correlation was applied for correlation of oxidative stress and lipid parameters. The p-value less than 0.05 was considered statistically significant. Results: The present study revealed that TNF-α 308G/A polymorphism was associated with RA (OR=1.9, p=0.02). Significant dyslipidemia, higher MDA and GST levels with decreased GSH and FRAP was observed in RA cases. RA cases with AA genotype presented with significantly higher levels of TNF-α, anti-CCP, CRP, MDA and GST. Plasma levels of TNF-α exhibited a positive correlation with ESR levels (r=0.22, p<0.05) and anti-CCP levels (r=0.21, p<0.05) whereas, MDA was positively correlated with Low-Density Lipoprotein (LDL-C) (r=0.32, p<0.05). Conclusion: The present study establishes that TNF α-308GA polymorphism was positively associated with rheumatoid arthritis and played a crucial role in its development and progression. Screening for genetic polymorphisms can help in identification of the susceptible population, development of personalised

Keywords

• inflammatory biomarkers
• lipid profile
• oxidant-antioxidant levels
• single nucleotide polymorphism