%0 Journal Article
%T IFNGR1 single nucleotide polymorphisms in rheumatoid arthritis
%A Stefan Mattyasovszky
%A Alla Skapenko
%A Joachim R Kalden
%A Peter E Lipsky
%A Hendrik Schulze-Koops
%J Arthritis Research & Therapy
%D 2006
%I BioMed Central
%R 10.1186/ar1927
%X Many pathologic autoimmune responses are characterized by an imbalance in the T helper type (Th) 1/Th2 ratio in favor of the former [1]. As activated Th1 cells mediate their functions via their signature cytokine, interferon gamma (IFN¦Ã), the interferon gamma receptor (IFN¦ÃR) plays an important role in the pathogenesis of these diseases by transmitting IFN¦Ã signaling. The IFN¦ÃR consists of the ligand-binding chain IFN¦ÃR1 and the signal-transducing chain IFN¦ÃR2. Within the coding region of the IFGR1 gene [GeneBank accession number NM_000416], two single nucleotide polymorphisms (SNPs) (40 C/T and 1,400 T/C) that result in the amino acid substitutions valine to methionine at position 14 (V467M) and leucine to proline at position 467 (L467P), respectively, have been identified in the Japanese population [2,3].Th1 cells have been implicated in many aspects of the pathogenesis of rheumatoid arthritis (RA) [1]. Evidence suggests that both genetic and environmental factors contribute to the development of rheumatoid inflammation [4-6]. Elucidating the genetic basis of RA, however, is still one of the major challenges in modern rheumatology. The identification of RA susceptibility genes has been difficult because RA is a complex autoimmune disease that, unlike classic Mendelian traits causally related to highly penetrant rare mutations of single genes, appears to be caused by small individual effects of many poorly penetrant common alleles.The association of the two IFNGR1 SNPs 40 C/T and 1,400 T/C with susceptibility to immune disorders mediated by an imbalance in the Th1/Th2 ratio has recently been demonstrated in Japanese cohorts; for example, in allergy [2] and in systemic lupus erythematosis [3,7]. Because of the potential importance of IFNGR1 SNPs in immunity in health and disease in people of all ethnic origins, these observations prompted us to perform a case-control association study to investigate the role of both IFNGR1 SNPs in susceptibility to RA, a Th1-mediate
%U http://arthritis-research.com/content/8/3/R63