title: T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status.
abstract: The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Department of Immunology, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Churl Hyun
authors.initials: CH
authors.lastname: Im
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Yun Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Kyungsook
authors.initials: K
authors.lastname: Park
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012984:Software; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000939:Epitopes; C448908:HAVCR2 protein, human; D006680:HLA Antigens; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins