Arg972 insulin receptor substrate-1 polymorphism and risk and severity of rheumatoid arthritis.

Aim: To explore the association between the Arg(972) insulin receptor substrate (IRS)-1 polymorphism (rs1801278) and the risk and disease activity/severity of rheumatoid arthritis (RA).

Method: We genotyped the Arg(972) IRS-1 polymorphism in 871 pairs of age-, sex-, body mass index-, residence area- and current smoking status-matched RA patients and controls. We assessed RA severity using the disease activity score of 28 joints (DAS28).

Results: The AA (homozygous Arg(972) IRS-1) and GA (heterozygous Arg(972) IRS-1) genotypes were significantly associated with high risk of RA with or without adjustment for comorbidities (P < 0.001). The A allele was significantly associated with high risk of RA (P < 0.001). The AA genotype was significantly associated with high/severe RA activity (P < 0.001), while the GG genotype (wild type IRS-1) had protective effects.

Conclusion: The Arg(972) IRS-1 polymorphism is associated with increased risk and disease activity/severity of RA, and therefore may be a potential prognostic factor for RA. This study adds novel insights into the pathogenesis of RA.