ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1762

Association of ETS1 Polymorphism in 3’ Untranslated Region with Susceptibility to Granulomatosis with Polyangiitis and Proteinase 3-ANCA Positive Vasculitis in a Japanese Population

Aya Kawasaki1, Keita Yamashita2, Fumio Hirano3, Ken-ei Sada4, Daisuke Tsukui5, Yuya Kondo6, Yoshitaka Kimura5, Kurumi Asako5, Shigeto Kobayashi7, Hidehiro Yamada8, Hiroshi Furukawa1, Kenji Nagasaka9, Takahiko Sugihara10, Kunihiro Yamagata11, Takayuki Sumida6, Shigeto Tohma12, Hajime Kono5, Shoichi Ozaki8, Seiichi Matsuo13, Hiroshi Hashimoto14, Hirofumi Makino15, Yoshihiro Arimura16, Masayoshi Harigai17 and Naoyuki Tsuchiya1, 1Molecular and Genetic Epidemiology Laboratory, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 2Molecular and Genetic Epidemiology, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 3Departments of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 4Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 5Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan, 6Department of Internal Medicine, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 7Department of Internal Medicine, Juntendo University Koshigaya Hospital, Koshigaya, Japan, 8Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 9Department of Rheumatology, Ome Municipal General Hospital, Ome, Japan, 10Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, 11Department of Nephrology, University of Tsukuba, Faculty of Medicine, Tsukuba, Japan, 12Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan, 13Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 14Juntendo University School of Medicine, Tokyo, Japan, 15Okayama University Hospital, Okayama, Japan, 16First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan, 17Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , ,

Session Information

Date: Monday, November 6, 2017

Title: Vasculitis Poster II: ANCA-Associated Vasculitis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: ETS Proto-oncogene 1, transcription factor (ETS1) is a transcription factor involved in immune responses. Genome-wide association studies on systemic lupus erythematosus (SLE) in Chinese populations identified the association of ETS1 polymorphism in 3’ untranslated region, rs1128334 A allele, which was associated with lower ETS1 expression. Recent studies indicated that many susceptibility genes are shared by multiple autoimmune diseases. In this study, we examined whether ETS1is associated with ANCA-associated vasculitis (AAV) in a Japanese population.

Methods: Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099 healthy controls by logistic regression analysis under the additive model. AAV patients were classified into 285 microscopic polyangiitis (MPA), 92 granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33 unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm. Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. Expression levels in ETS1 mRNA in the whole peripheral blood were compared between 8 AAV patients and 14 healthy controls.

Results: When the patients were classified according to the EMEA classification, rs1128334 A was significantly increased in GPA (P=0.0060, Pc=0.030, odds ratio [OR] 1.54, 95% confidence interval [CI] 1.13-2.10) when compared with healthy controls. With respect to the ANCA specificity, significant association was observed in PR3-ANCA positive AAV (P=0.0042, Pc=0.021, OR 1.72, 95% CI 1.19-2.49). Expression analysis indicated that ETS1 mRNA levels were decreased in AAV (P=0.0024).

Conclusion: ETS1 polymorphism was suggested to be associated with susceptibility to GPA and PR3-ANCA positive AAV in a Japanese population.

Table 1. Association of ETS1 polymorphism with AAV in a Japanese population.

ETS1 rs1128334

A/A

A/G

G/G

A allele

P

Pc

OR(95%CI)

EMEA classification

GPA(n=92)

20(0.217)

50(0.543)

22(0.239)

90(0.489)

0.0060

0.030

1.54

(1.13-2.10)

MPA(n=285)

53(0.186)

138(0.484)

94(0.330)

244(0.428)

0.072

0.36

1.19

(0.98-1.44)

EGPA(n=56)

7(0.125)

30(0.536)

19(0.339)

44(0.393)

0.90

1.0

1.03

(0.69-1.52)

ANCA specificity

PR3-AAV(n=62)

17(0.274)

30(0.484)

15(0.242)

64(0.516)

0.0042

0.021

1.72

(1.19-2.49)

MPO-AAV(n=376)

68(0.181)

188(0.500)

120(0.319)

324(0.431)

0.032

0.16

1.20

(1.02-1.43)

Healthy controls(n=1099)

156(0.142)

539(0.490)

404(0.368)

851(0.387)

Disclosure: A. Kawasaki, None; K. Yamashita, None; F. Hirano, Chugai Pharmaceutical Co., Ltd.; Ono Pharmaceuticals; Mitsubishi Tanabe Pharma Co.; UCB Japan; CSL Behring; Towa Pharmaceutical Co., Ltd.; Abbvie Japan Co., Ltd.; Japan Blood Products Organization; Ayumi Pharmaceutical Co.; and Nippon Kayaku Co., Ltd, 3,Astellas Pharma Inc, 5; K. E. Sada, None; D. Tsukui, None; Y. Kondo, None; Y. Kimura, None; K. Asako, None; S. Kobayashi, None; H. Yamada, None; H. Furukawa, Bristol-Myers Squibb Co., 2,Ayumi Pharmaceutical Corporation, 5; K. Nagasaka, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb K.K., Teijin Pharma Ltd., Actelion Pharmaceuticals Ltd., Ayumi Pharmaceutical Co., Ltd.., 5; T. Sugihara, Takeda Pharmaceutical Co. Ltd., Mitsubishi-Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Co., Ltd., UCB Japan Co. Ltd, Astellas Pharma Inc., Janssen Pharmaceutical K.K., Pfizer Japan Inc., and Bristol Myers Squibb K.K, 5; K. Yamagata, None; T. Sumida, None; S. Tohma, None; H. Kono, None; S. Ozaki, None; S. Matsuo, None; H. Hashimoto, None; H. Makino, None; Y. Arimura, None; M. Harigai, Eisai Ltd, Takeda Ltd, Teijin, 2,Eli Lilly and Company, BMS, Chugai, Janssen, 5; N. Tsuchiya, Novartis Pharmaceutical Corporation, 2,Ayumi Pharmaceutical Co, 5.

To cite this abstract in AMA style:

Kawasaki A, Yamashita K, Hirano F, Sada KE, Tsukui D, Kondo Y, Kimura Y, Asako K, Kobayashi S, Yamada H, Furukawa H, Nagasaka K, Sugihara T, Yamagata K, Sumida T, Tohma S, Kono H, Ozaki S, Matsuo S, Hashimoto H, Makino H, Arimura Y, Harigai M, Tsuchiya N. Association of ETS1 Polymorphism in 3’ Untranslated Region with Susceptibility to Granulomatosis with Polyangiitis and Proteinase 3-ANCA Positive Vasculitis in a Japanese Population [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/association-of-ets1-polymorphism-in-3-untranslated-region-with-susceptibility-to-granulomatosis-with-polyangiitis-and-proteinase-3-anca-positive-vasculitis-in-a-japanese-population/. Accessed .

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