Background/Purpose:
In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), geographic difference in the type of vasculitis is well known. While granulomatosis with polyangiitis (GPA) is the most common form of AAV in northern European populations, microscopic polyangiitis (MPA) accounts for the majority of AAV in Japan, suggesting that the genetic background may play a role in the occurrence of these diseases. Due to low prevalence in European populations, little is known on the genetics of MPA or myeloperoxidase (MPO)-ANCA positive vasculitis. We started a multicenter collaborative study on the genetics of AAV in a Japanese population in 1999. Thus far, we reported a significant association of HLA-DRB1*09:01 with MPA. HLA-DRB1*09:01, one of the most common HLA-DRB1 alleles in the Asian but rare in the Caucasian populations, has been shown to be associated with multiple autoimmune diseases in Japan.
We have also demonstrated that STAT4, IRF5 and BLK were associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc) in a Japanese population, indicating that these genes are shared susceptibility genes to multiple autoimmune diseases. Thus far, association between these genes and MPA or MPO-ANCA positive vasculitis has not been reported. In this study, we examined association of these genes with Japanese AAV, mainly consisting of MPO-ANCA positive vasculitis.
Methods:
Association of STAT4 rs7574865, IRF5 rs2280714 and BLK rs13277113, all previously shown to be associated with other autoimmune diseases in a Japanese population, was examined in 177 Japanese patients with AAV including 127 MPA, 31 GPA and 14 eosinophilic granulomatosis with polyangiitis (EGPA), as well as in 511 healthy individuals. Among the patients, 155 were positive for MPO-ANCA. The genotypes were determined using TaqMan genotyping assay and direct sequencing.
Results:
The frequency of STAT4 rs7574865 T/T genotype, the risk genotype for SLE, RA and SSc, was significantly increased in MPO-ANCA positive patients (18.7%) as compared with healthy controls (10.4%, P=0.0058, odds ratio [OR] 1.98, 95% condidence interval [CI] 1.22-3.23). A tendency toward association was also observed in MPA (16.5%, P=0.053, OR 1.71, 95%CI 0.99-2.94), GPA (P=0.12, OR 2.07, 95%CI 0.83-5.18) and EGPA (P=0.013, OR 4.79, 95%CI 1.71-13.4).
With respect to IRF5, rs2280714 A allele showed a tendency toward decrease in MPA, although the difference did not reach statistical significance (A allele frequency in MPA: 49.2%, controls: 55.5%, P=0.072, OR 0.78, 95%CI 0.59-1.02). No evidence for association of BLK was detected.
Conclusion:
STAT4 rs7574865 T/T was associated with MPO-ANCA positive vasculitis. Our observations suggested that STAT4 is a shared susceptibility gene for SLE, RA, SSc and AAV.
Disclosure:
A. Kawasaki,
None;
N. Inoue,
None;
C. Ajimi,
None;
I. Ito,
None;
K. E. Sada,
None;
S. Kobayashi,
None;
H. Yamada,
None;
H. Furukawa,
None;
M. Tomita,
None;
T. Sumida,
None;
S. Tohma,
Pfizer Japan lnc., Eisai Co.,Ltd, Chugai Pharmaceutical Co.，Ltd,
2;
N. Miyasaka,
None;
S. Ozaki,
None;
H. Hashimoto,
None;
H. Makino,
None;
M. Harigai,
Teijin Pharma Limited,
5;
N. Tsuchiya,
None.
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-background-of-antineutrophil-cytoplasmic-antibody-associated-vasculitis-in-a-japanese-population-association-of-stat4-with-myeloperoxidase-antineutrophil-cytoplasmic-antibody-positive-vasculi/