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Advances in the genomics of ANCA-associated vasculitis—a view from East Asia

Abstract

Recent genome-wide association studies (GWAS) in populations of European ancestry have identified several susceptibility genes to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The most significant association was observed in HLA-DP variants in granulomatosis with polyangiitis and proteinase 3 (PR3)-ANCA positive vasculitis, while HLA-DQ variants were strongly associated with microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA positive vasculitis (MPO-AAV). In non-HLA genes, SERPINA1, PRTN3 and PTPN22 were identified as susceptibility genes to AAV. The observations in GWAS suggested the presence of shared and non-shared susceptibility genes among AAV subsets. Epidemiological features of AAV are strikingly different in the East Asian populations; the proportions of MPO-AAV among total AAV, MPO-ANCA positive patients among GPA, and patients with interstitial lung disease among total AAV are considerably higher in Japan as compared with Europe. Such population differences suggest the critical role for genetic background behind these conditions. Although no GWAS has been reported in the Asian populations so far, the association of HLA-class II alleles with MPA and MPO-AAV was identified. Future genomics studies on AAV, especially from Asian populations, will provide valuable information to elucidate the molecular mechanisms and to identify molecular targets for AAV.

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Fig. 1: Susceptibility genes/regions reported in genome-wide association studies on ANCA-associated vasculitis.
Fig. 2: HLA-class II variants associated with ANCA-associated vasculitis.

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Acknowledgements

We are grateful to Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) and the Japan Agency for Medical Research and Development for supporting our studies discussed in this review.

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Correspondence to Naoyuki Tsuchiya.

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AK has received research grants from SENSHIN Medical Research Foundation, the Takeda Science Foundation, and the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care. NT has received research fund from H.U. Group Research Institute for a collaborative research, and research grants from Bristol-Myers Squibb, The Naito Foundation, Mitsubishi Tanabe Pharma, 2015 Japan College of Rheumatology Award from Japan College of Rheumatology, 2017 Novartis Rheumatology Award from Japan Rheumatism Association with research funding, and speaker’s honoraria from Teijin.

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Kawasaki, A., Tsuchiya, N. Advances in the genomics of ANCA-associated vasculitis—a view from East Asia. Genes Immun 22, 1–11 (2021). https://doi.org/10.1038/s41435-021-00123-x

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