Genetic background of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: association of HLA-DRB1*0901 with microscopic polyangiitis.
OBJECTIVE
To examine association of 8 candidate genes with susceptibility to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japanese patients. Little is known on the genetic background of AAV in Japanese patients mainly because of the difficulty in collecting a sufficient number of samples for the genetics study.


METHODS
Sixty-nine patients, including 50 with microscopic polyangiitis (MPA), were recruited in a multicenter study. Among them, 64 patients were positive for myeloperoxidase (MPO)-ANCA. Associations of HLA-DRB1, tumor necrosis factor-alpha promoter (TNF), TNF receptor 2 (TNFR2), Fcgamma receptor IIa (FCGR2A), IIb (FCGR2B), IIIa (FCGR3A), IIIb (FCGR3B), and CTLA-4 (CTLA4) polymorphisms were examined in a case-control analysis.


RESULTS
A significant association of HLA-DRB1*0901 with MPA (p = 0.0037, OR 2.44, 95% CI 1.33-4.46), as well as with MPO-ANCA positivity (p = 0.0014, OR 2.44, 95% CI 1.41-4.22), was detected. There was no difference in the TNF promoter haplotype frequencies between patients with MPA and controls, excluding the possibility that the association of DRB1*0901 was secondarily caused by linkage disequilibrium with TNF. No association was observed for TNFR2, FCGR, or CTLA4 with MPA, nor with the presence of MPO-ANCA, although the combined genotype FCGR2A-131H/H and 3A-176F/F was increased in patients with MPA (p = 0.025).


CONCLUSIONS
There was an association of HLA-DRB1*0901 with MPA and MPO-ANCA positive vasculitis in Japanese patients.
Tsuchiya
Naoyuki
N
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. tsuchiya-tky@umin.ac.jp
Kobayashi
Shigeto
S
Kawasaki
Aya
A
Kyogoku
Chieko
C
Arimura
Yoshihiro
Y
Yoshida
Masaharu
M
Tokunaga
Katsushi
K
Hashimoto
Hiroshi
H
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014657:Vasculitis / Q000097:blood / Q000235:genetics* / Q000473:pathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D009195:Peroxidase