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RISS 인기검색어
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- 저자 : Momozawa, Y. (검색결과 1 건)
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Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis
Okada, Y.,Suzuki, A.,Ikari, K.,Terao, C.,Kochi, Y.,Ohmura, K.,Higasa, K.,Akiyama, M.,Ashikawa, K.,Kanai, M.,Hirata, J.,Suita, N.,Teo, Y.Y.,Xu, H.,Bae, S.C.,Takahashi, A.,Momozawa, Y.,Matsuda, K.,Momoh University of Chicago Press [etc.] 2016 American journal of human genetics Vol.99 No.2
<P>Despite the progress in human leukocyte antigen (HLA) causal variant mapping, independent localization of major histocompatibility complex (MHC) risk from classical HLA genes is challenging. Here, we conducted a large-scale MHC fine-mapping analysis of rheumatoid arthritis (RA) in a Japanese population (6,244 RA cases and 23,731 controls) population by using HLA imputation, followed by a multi-ethnic validation study including east Asian and European populations (n=7,097 and 23,149, respectively). Our study identified an independent risk of a synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated protein autoantibody (ACPA)-positive RA risk (p=1.4 x 10(-) 9), which demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on HLA-DOA expression. Trans-ethnic comparison revealed different linkage disequilibrium (LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed HLA-DOA variant risk heterogeneity among ethnicities, which was most evident in the Japanese population. Although previous HLA fine-mapping studies have identified amino acid polymorphisms of the classical HLA genes as driving genetic susceptibility to disease, our study additionally identifies the dosage contribution of a non-classical HLA gene to disease etiology. Our study contributes to the understanding of HLA immunology in human diseases and suggests the value of incorporating additional ancestry in MHC fine-mapping.</P>
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