The association between TNFα gene polymorphisms and susceptibility to rheumatoid arthritis in an ethnic Kashmiri population: relationship with disease activity and severity markers

Aim: The aim of our study was to determine the genetic associations between polymorphisms of the TNF alpha gene (-308G/A and -238G/A) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in an ethnic Kashmiri population. Methods: Allele and genotype frequencies of TNF alpha-308G/A and TNF alpha-238G/A polymorphisms were compared between 150 RA patients and 200 healthy controls by using polymerase chain reaction - restriction fragment length polymorphism method. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) was also assessed. Results: We did not find any significant association between TNF alpha-308G/A and TNF alpha-238G/A polymorphism and RA risk (P > 0.05), but TNF alpha-308GG genotype was associated significantly with rheumatoid factor seropositivity (P < 0.01) and TNF alpha-238GA genotype was associated with swollen joint count < 5 (P = 0.04) as well as with less severe disease activity as measured by DAS28 score (P = 0.02). Conclusion: Our findings suggest the possible roles of TNF alpha-308GG and TNF alpha-238GA as important determinants for the development of certain manifestations and disease severity in RA in ethnic Kashmiri population.