title: Genetics of ANCA-associated vasculitis in Japan: a role for HLA-DRB1*09:01 haplotype.
abstract: The epidemiology of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is considerably different between European and Asian populations. Whereas granulomatosis with polyangiitis is the most common form of AAV in northern European populations, microscopic polyangiitis (MPA) accounts for the majority of AAV in Japan. This difference may at least in part derive from the difference in genetic background. In this review, I focus on our observation on HLA, an obvious candidate gene for immune disorders, and discuss its potential implication. In Japanese AAV, significant association was detected with HLA-DRB1*09:01, the carrier frequency of which was increased in MPA [P=0.0087, odds ratio (OR) 1.90, 95% confidence interval (CI) 1.17-3.08] and in myeloperoxidase (MPO)-ANCA-positive AAV (P=0.0016, OR 2.05, 95% CI 1.31-3.23) when compared with healthy Japanese controls. HLA-DRB1*09:01 is one of the most common HLA-DRB1 alleles in Asians but is rare in Caucasian populations. Interestingly, HLA-DRB1*09:01 has been shown to be associated with multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, suggesting that either HLA-DRB1*09:01 itself or other genes in tight linkage disequilibrium may play a role in a molecular pathway shared by various autoimmune diseases in Japanese and possibly in other Asian populations.
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. tsuchiya-tky@umin.net.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors
chemical_list: D059811:HLA-DRB1 Chains; C487381:HLA-DRB1*09:01 antigen