Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed.The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity.We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.Rheumatoid arthritis (RA) is a severely disabling chronic inflammatory disease that affects millions of people worldwide. Like in other autoimmune diseases females are affected more often than males. The disease course differs widely between patients. While some have low grade disease which is easily controlled by therapy with one disease-modifying anti-rheumatic drug (DMARD), others suffer from rapidly progressive disease with erosions that is therapy resistant, resulting in the use of many different DMARDs or even the need for therapy with the new biologicals directed against TNF-α. Cytokines and other proteins involved in the inflammatory response play a role in RA. Pro-inflammatory cytokines such as TNF-α and IL-1β are regarded as key players in the pathogenesis of RA [1,2]. This is further underlined by the development of several anti-cytokine drugs in the treatment of RA, with anti-TNF monoclonal antibodies and soluble TNF-α receptor being the most effective. TNF-α