Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Epidemiology of ANCA-associated vasculitis (AAV) is substantially different between East Asian and European populations. Microscopic polyangiitis (MPA) and MPO-ANCA positive AAV (MPO-AAV) are prevalent in Japan, while granulomatosis with polyangiitis (GPA) and PR3-ANCA positive AAV (PR3-AAV) are dominant in Europe. In addition, high prevalence of interstitial lung disease (ILD), a severe complication and a prognostic factor in AAV, is a striking feature in the Japanese population, suggesting a role for genetic background in the development and clinical features of AAV.
A proportion of patients with idiopathic pulmonary fibrosis (IPF) are positive for MPO-ANCA, and some of these patients develop MPA, suggesting that ILD in AAV and IPF may share some pathogenic processes. Recently, we reported that 5% of MPO-AAV patients with ILD carry MUC5B single nucleotide variant (SNV) rs35705950T, the risk allele for IPF, as compared with 1% among healthy controls, indicating that MUC5B is a shared susceptibility gene between IPF and MPO-AAV associated ILD (Namba et al, Ann Rheum Dis 2019). However, the allele frequency of rs35705950T is much lower in general Japanese population as compared with European populations, and does not account for high prevalence of ILD in Japanese AAV. In this study, we performed association study of other IPF susceptibility genes, TERT and DSP, to examine whether these are associated with ILD in AAV patients.
Methods: The members of Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) and Research Committee of Progressive Renal Disease, Ministry of Health, Labour, and Welfare of Japan contributed to this study.
Five hundred and twenty-three patients including 315 MPA, 108 GPA, 68 eosinophilic granulomatosis with polyangiitis (EGPA) and 32 unclassifiable AAV (412 MPO-ANCA positive [MPO-AAV] and 66 PR3-ANCA positive [PR3-AAV]) and 4394 controls were examined. Among MPO-AAV, 163 were positive for ILD and 264 were negative. Genotyping for TERT rs2736100 and DSP rs2076295 was performed by TaqMan SNP Genotyping Assays. Association was tested by chi-squared test.
Results: Allele frequencies of TERT rs2736100A and DSP rs2076295G were not significantly different between MPO-AAV with ILD and MPO-AAV without ILD (Table 1). However, when the association of TERT was tested in MPO-AAV regardless of the presence/absence of ILD, rs2736100A was significantly increased in MPO-AAV as compared with healthy controls (P=4.3E-05, Pc=5.2E-04, odds ratio [OR] 1.37). This association was also observed in MPA (P=2.2E-04, Pc=0.0013, OR 1.38). Similarly, DSP rs2076295G is increased in MPA (P=0.0029, Pc=0.0086, OR 1.28) and MPO-AAV (P=0.0026, Pc=0.0086, OR 1.25) as compared with healthy controls. Other AAV phenotypes were not significantly associated with both SNVs after correction for multiple testing, although a trend for association was observed between EGPA and TERT and between PR3-AAV and DSP.
Conclusion: TERT and DSP SNVs were found to be associated with MPO-AAV and MPA for the first time. These results suggest that some susceptibility genes to IPF may be associated with AAV regardless of the presence of ILD.
To cite this abstract in AMA style:Kawasaki A, Namba N, Sada K, Hirano F, Kobayashi S, Yamada H, Furukawa H, Nagasaka K, Sugihara T, Suzuki A, Yamagata K, Sumida T, Tohma S, Homma S, Ozaki S, Hashimoto H, Makino H, Arimura Y, Harigai M, Tsuchiya N. Association of TERT and DSP Polymorphisms with Susceptibility to Myeloperoxidase-ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/association-of-tert-and-dsp-polymorphisms-with-susceptibility-to-myeloperoxidase-anca-associated-vasculitis/. Accessed November 28, 2020.
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