ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 85

Protective Association of HLA-DRB1*13:02 Against MPO-ANCA Positive ANCA-Associated Vasculitis in a Japanese Population

Naoyuki Tsuchiya1, Narumi Hasebe1, Ken-ei Sada2, Shigeto Kobayashi3, Hidehiro Yamada4, Hiroshi Furukawa5, Kunihiro Yamagata6, Takayuki Sumida7, Nobuyuki Miyasaka8, Seiichi Matsuo9, Shigeto Tohma5, Shoichi Ozaki10, Hiroshi Hashimoto11, Hirofumi Makino2, Masayoshi Harigai12 and Aya Kawasaki1, 1Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 2Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 3Department of Internal Medicine, Juntendo University Koshigaya Hospital, Tokyo, Japan, 4Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 5Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan, 6Department of Internal Medicine (Nephrology), Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 7Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 8Department of Medicine and Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan, 9Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 10Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 11Juntendo University School of Medicine, Tokyo, Japan, 12Department of Pharmacovigilance, Tokyo Medical and Dental University, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Genetics, Genomics and Proteomics I

Session Type: Abstract Submissions (ACR)

Background/Purpose

Epidemiology of antineutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV) is substantially different between European and Asian populations. In the Japanese population, the majority of AAV patients are positive for myeloperoxidase (MPO) – ANCA. In studies with a small sample size, we previously reported significant association of HLA-DRB1*09:01-DQB1*03:03, a haplotype common in Asians but rare in other populations, with MPO-ANCA positive AAV (Tsuchiya et al., 2003; Tsuchiya et al., 2006). In the present study, we substantially increased the sample size, and compared HLA-DRB1 associations among AAV subgroups, and also made an attempt to detect other DRB1alleles associated with risk or protection.

Methods

HLA-DRB1genotypes were determined by using WAK Flow HLA-typing kit (Wakunaga, Hiroshima, Japan) in 356 Japanese AAV and 596 healthy controls. Among the patients, 220 were classified as microscopic polyangiitis (MPA), 69 as granulomatosis with polyangiitis (GPA), 35 as eosinophilic granulomatosis with polyangiitis (EGPA), and 32 were unclassifiable, according to the European Medicines Agency algorithm. Among all patients, 300 were positive for myeloperoxidase (MPO)-ANCA and 41 for proteinase 3 (PR3)-ANCA. The second risk allele and protective allele were examined by relative predispositional effects (RPE) method. Bonferroni correction was employed to correct for the number of compared alleles.

Results

Positive association of DRB1*09:01 carrier frequency was confirmed in MPA (P=0.0036, Pc=0.0076, odds ratio [OR] 1.81). In addition, significant negative association with DRB1*13:02 was detected in MPA (P=0.001, Pc=0.0244, OR 0.43). In GPA, tendency toward positive association was detected in DRB1*08:02 (P=0.031, Pc=0.65, OR 2.56) and negative association in DRB1*13:02 (P=0.037, Pc=0.77, OR 0.38). The associations were more striking when the patients were classified according to the specificity of ANCA. In MPO-ANCA positive patients, DRB1*09:01 was increased (P=2.3×10-5, Pc=4.8×10-4, OR 1.89), while DRB1*13:02 was decreased (P=3.7×10-5, Pc=7.8×10-4, OR 0.38). RPE method confirmed negative association of DRB1*13:02 (PRPE=7.3×10-4, ORRPE 0.47), and also suggested DRB1*08:02 as the second risk allele (PRPE=0.025, ORRPE 1.82). In PR3-ANCA positive patients, suggestive association was observed for DRB1*11:01 (P=0.021, Pc=0.65, OR 3.80), but not for DRB1*09:01 (P=0.86, OR 1.02). Genotype comparison suggested that carriage of DRB1*13:02 cancels the risk of DRB1*09:01 to MPO-ANCA positive AAV in *09:01/*13:02 heterozygotes.

Conclusion

DRB1*09:01 is associated with MPO-ANCA positive, but not with PR3-ANCA positive, AAV. Because DRB1*09:01 is a very common HLA-DRB1 allele in East Asian bur rare in European populations, such a difference in the genetic background may be associated with the difference in the prevalence of MPO-positive and PR3-positive AAV in both populations. In addition, DRB1*13:02 was identified as a protective allele against MPO-ANCA positive AAV.

Disclosure:

N. Tsuchiya,
None;

N. Hasebe,
None;

K. E. Sada,
None;

S. Kobayashi,
None;

H. Yamada,
None;

H. Furukawa,
None;

K. Yamagata,
None;

T. Sumida,
None;

N. Miyasaka,
None;

S. Matsuo,
None;

S. Tohma,
None;

S. Ozaki,
None;

H. Hashimoto,
None;

H. Makino,
None;

M. Harigai,
None;

A. Kawasaki,
None.

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/protective-association-of-hla-drb11302-against-mpo-anca-positive-anca-associated-vasculitis-in-a-japanese-population/