title: Arg972 insulin receptor substrate-1 polymorphism and risk and severity of rheumatoid arthritis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Long
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: You
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D065840:Protective Factors; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins
keywords: disease activity score of 28 joints (DAS28); gene polymorphism; insulin receptor substrate-1; insulin resistance; rheumatoid arthritis