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This study was carried out to elucidate the role of cytokine genes in the pathogenesis of RA in Kashmiri population. We found a significant association between IL1beta -511T/C polymorphism and the occurance of RA. However, our results indicated that the polymorphisms in the TNF- promoter region ,IL1beta +3954C/T and IL-6 -174G/C may not confer risk of developing RA in our Kashmiri population but the presence of the risk alleles in a particular patient may contribute to the disease severity and hence to altered response to the biological agents. We also found RA to be associated with the high expression of TNF- , IL-1beta and IL-6 cytokines in our Kashmiri population. We suggest that with increasing interest in cytokine directed therapy, knowledge of each individual's cytokine profile may contribute to the logical choice of these potentially highly effective, but very expensive treatments.