Genotyping of relapsing polychondritis identified novel susceptibility HLA alleles and distinct genetic characteristics from other rheumatic diseases
Autor: | Hajime Yoshifuji, Taira Maekawa, Koichiro Ohmura, Hiroshi Handa, Hiroto Kojima, Kimiko Yurugi, Hiroh Saji, Tsuneyo Mimori, Yoshihisa Yamano, Fumihiko Matsuda, Yasuo Miura, Chikashi Terao |
---|---|
Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine Linkage disequilibrium Genotype Human leukocyte antigen Linkage Disequilibrium 03 medical and health sciences 0302 clinical medicine Rheumatology Rheumatic Diseases HLA-B Antigens HLA-DQ beta-Chains Humans Medicine Genetic Predisposition to Disease Pharmacology (medical) Polychondritis Relapsing Age of Onset Allele Genetic association 030203 arthritis & rheumatology Genetics HLA-DQB1 business.industry Haplotype 030104 developmental biology Immunology Female sense organs business HLA-DRB1 Chains |
Zdroj: | Rheumatology. 55:1686-1692 |
ISSN: | 1462-0332 1462-0324 |
Popis: | Objective To uncover the genetic background of relapsing polychondritis (RPC), a rare autoimmune disease with unknown mechanisms characterized by systemic inflammation of the cartilage, to deepen our understanding of the pathophysiology of RPC and show its distinct genetic characteristics from other rheumatic diseases. Methods A total of 102 patients with RPC and 1000 healthy subjects were recruited for a two-staged genetic association study and genotyped for six HLA classical loci. Haplotype association tests were also performed. The associations of amino acid (AA) residues and positions with susceptibility to RPC were analysed. Frequencies of representative susceptibility HLA alleles to other rheumatic diseases in RPC were also analysed. Results HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, which are in linkage disequilibrium with each other, were associated with RPC (P = 1.9 × 10(-6), 1.4 × 10(-5) and 0.00024, respectively). AA residue at position 57 in HLA-DQB1, the most significant position in type I diabetes mellitus, showed the strongest association among AA residues. HLA-DR4, a known susceptibility allele in Germans, showed a trend of susceptibility association without significance (P = 0.067). No associations were observed between the three alleles and clinical phenotypes. Representative susceptibility HLA alleles to RA, SLE, Behcet disease and Takayasu arteritis did not show enrichment in RPC in spite of sufficient statistical power. Conclusions HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, in linkage disequilibrium with each other, are associated with susceptibility to RPC Importance of HLA-class II loci in RPC susceptibility is suggested. RPC is considered a genetically distinct disease from other rheumatic diseases. |
Databáze: | OpenAIRE |
Externí odkaz: |