Association of TERT and DSP variants with microscopic polyangiitis and myeloperoxidase-ANCA positive vasculitis in a Japanese population: a genetic association study

Aya Kawasaki, Natsumi Namba, Ken ei Sada, Fumio Hirano, Shigeto Kobayashi, Kenji Nagasaka, Takahiko Sugihara, Nobuyuki Ono, Takashi Fujimoto, Makio Kusaoi, Naoto Tamura, Kunihiro Yamagata, Takayuki Sumida, Hiroshi Hashimoto, Shoichi Ozaki, Hirofumi Makino, Yoshihiro Arimura, Masayoshi Harigai, Naoyuki Tsuchiya

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8 Citations (Scopus)


Background: Interstitial lung disease (ILD) is a severe complication with poor prognosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Prevalence of AAV-associated ILD (AAV-ILD) in Japan is considerably higher than that in Europe. Recently, we reported that a MUC5B variant rs35705950, the strongest susceptibility variant to idiopathic pulmonary fibrosis (IPF), was strikingly increased in AAV-ILD patients but not in AAV patients without ILD; however, due to the low allele frequency in the Japanese population, the MUC5B variant alone cannot account for the high prevalence of AAV-ILD in Japan. In this study, we examined whether other IPF susceptibility alleles in TERT and DSP genes are associated with susceptibility to AAV subsets and AAV-ILD. Methods: Five hundred and forty-four Japanese patients with AAV and 5558 controls were analyzed. Among the AAV patients, 432 were positive for myeloperoxidase (MPO)-ANCA (MPO-AAV). A total of 176 MPO-AAV patients were positive and 216 were negative for ILD based on CT or high-resolution CT. Genotypes of TERT and DSP variants were determined by TaqMan SNP Genotyping Assay, and their association was tested by chi-square test. Results: When the frequencies of the IPF risk alleles TERT rs2736100A and DSP rs2076295G were compared between AAV subsets and healthy controls, both alleles were significantly increased in microscopic polyangiitis (MPA) (TERT P = 2.3 × 10−4, Pc = 0.0023, odds ratio [OR] 1.38; DSP P = 6.9 × 10−4, Pc = 0.0069, OR 1.32) and MPO-AAV (TERT P = 1.5 × 10−4, Pc = 0.0015, OR 1.33; DSP P = 0.0011, Pc = 0.011, OR 1.26). On the other hand, no significant association was detected when the allele frequencies were compared between MPO-AAV patients with and without ILD. Conclusions: Unexpectedly, TERT and DSP IPF risk alleles were found to be associated with MPA and MPO-AAV, regardless of the presence of ILD. These findings suggest that TERT and DSP may be novel susceptibility genes to MPA/MPO-AAV and also that some susceptibility genes may be shared between IPF and MPA/MPO-AAV.

Original languageEnglish
Article number246
JournalArthritis Research and Therapy
Issue number1
Publication statusPublished - Dec 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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