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 TNFα 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 TNFα-308G/A and TNFα-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 TNFα-308G/A and TNFα-238G/A polymorphism and RA risk (P > 0.05), but TNFα-308GG genotype was associated significantly with rheumatoid factor seropositivity (P < 0.01) and TNFα-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 TNFα-308GG and TNFα-238GA as important determinants for the development of certain manifestations and disease severity in RA in ethnic Kashmiri population.