Genetic Variations and Epigenetic Modifications of TNF-α in Rheumatoid Arthritis

Abstract

Background: Preceding studies have shown positive association of TNF- α polymorphism has been found in Caucasian population for RA. Similarly studies have been done to find association in inflammatory bowel disease in Caucasian population and osteoarthritis in Chinese population which has come up to be negative. Age related loss in methylation pattern has been observed in TNF promoter region while other studies have shown varied methylation pattern of genes including DR3, IL6, IL10 in rheumatoid arthritis. Methods: In this study, two polymorphisms (rs361525 and rs1800750) of TNFα located in the promoter region were studied in Pakistani population as case-control study through restriction fragment length-polymerase chain reaction (RFLP-PCR). Methylation status of TNF-α promoter was also investigated using Methylation specific and Un-methylation specific PCR after bisulfite conversion of genomic DNA. Results: The results showed that TNFα SNP rs361525 genotype had no association with disease susceptibility while significant association was found in the SNP rs1800750, the allele A was found to have a protective role in disease. Results showed statistically significant association of methylation status of the promoter to RA. Additional studies with larger and diverse populations are required to confirm current findings.