Abstract
Microscopic polyangiitis (MPA) is a rare and severe form of systemic necrotizing vasculitis associated with myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA). We previously reported significant association of HLA-DRB1*0901 with MPA. To define the susceptibility loci within the HLA region, we determined the genotypes of HLA-DQB1, DPB1, B and C in 50 patients with MPA and 77 unrelated Japanese controls. In addition to HLA-DRB1*0901, significant association of DQB1*0303 (allele carrier frequencies 50% in MPA, 29.9% in controls, odds ratio 2.35, P=0.017) was detected. These alleles were in strong linkage disequilibrium (D′=0.95, r2=0.82). Increased frequency was also observed for DPB1*0201, B*15111 and Cw*0303, which was at least partly accounted for by linkage disequilibrium with DRB1*0901 and DQB1*0303. These results indicate that DRB1*0901-DQB1*0303 haplotype represents the primary genetic risk for MPA within the HLA region in Japanese, and provides the basis that future functional studies on the role of HLA in MPA should target DR9, DQ9 and DR53 proteins encoded by this haplotype.
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Acknowledgements
The authors are indebted to the patients and healthy donors who participated in this study, to the doctors who recruited the patients, and to Aya Kawasaki (Department of Human Genetics, The University of Tokyo) for technical assistance. This study was supported by the Ministry of Health, Labour, and Welfare, the Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Society for the Promotion of Science (JSPS), and Takeda Science Foundation.
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Tsuchiya, N., Kobayashi, S., Hashimoto, H. et al. Association of HLA-DRB1*0901-DQB1*0303 haplotype with microscopic polyangiitis in Japanese. Genes Immun 7, 81–84 (2006). https://doi.org/10.1038/sj.gene.6364262
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DOI: https://doi.org/10.1038/sj.gene.6364262
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