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18. MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease

Author

Juge, P.-A. Lee, J.S. Ebstein, E. Furukawa, H. Dobrinskikh, E. Gazal, S. Kannengiesser, C. Ottaviani, S. Oka, S. Tohma, S. Tsuchiya, N. Rojas-Serrano, J. González-Pérez, M.I. Mejía, M. Buendía-Roldán, I. Falfán-Valencia, R. Ambrocio-Ortiz, E. Manali, E. Papiris, S.A. Karageorgas, T. Boumpas, D. Antoniou, K. Van Moorsel, C.H.M. Van Der Vis, J. De Man, Y.A. Grutters, J.C. Wang, Y. Borie, R. Wemeau-Stervinou, L. Wallaert, B. Flipo, R.-M. Nunes, H. Valeyre, D. Saidenberg-Kermanac'H, N. Boissier, M.-C. Marchand-Adam, S. Frazier, A. Richette, P. Allanore, Y. Sibilia, J. Dromer, C. Richez, C. Schaeverbeke, T. Lioté, H. Thabut, G. Nathan, N. Amselem, S. Soubrier, M. Cottin, V. Clément, A. Deane, K. Walts, A.D. Fingerlin, T. Fischer, A. Ryu, J.H. Matteson, E.L. Niewold, T.B. Assayag, D. Gross, A. Wolters, P. Schwarz, M.I. Holers, M. Solomon, J.J. Doyle, T. Rosas, I.O. Blauwendraat, C. Nalls, M.A. Debray, M.-P. Boileau, C. Crestani, B. Schwartz, D.A. Dieudé, P.

Abstract

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P = 9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P = 4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P = 1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P = 7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P = 2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. Copyright © 2018 Massachusetts Medical Society.

Published
2018

19. MUC5B PROMOTER VARIANT RS35705950 IS A RISK FACTOR FOR RHEUMATOID ARTHRITIS - INTERSTITIAL LUNG DISEASE

Author

Juge, P. -A. Lee, J. S. Ebstein, E. Furukawa, H. and Dobrinskikh, E. Gazal, S. Kannengiesser, C. Ottaviani, S. and Tsuchiya, N. Oka, S. Tohma, S. Rojas-Serrano, J. and Gonzalez-Perez, M. -I. Mejia, M. Buendia-Roldan, I. and Falfan-Valencia, R. Manali, E. Papiris, S. A. Karageorgas, T. Boumpas, D. Antoniou, K. Van Moorsel, C. van der Vis, J. de Man, Y. Grutters, J. Wang, Y. Borie, R. and Wemeau-Stervinou, L. Wallaert, B. Flipo, R. -M. Nunes, H. and Valeyre, D. Saidenberg, N. Marchand-Adam, S. Deane, K. and Walts, A. Fingerlin, T. Matteson, E. Niewold, T. and Assayag, D. Gross, A. Wolters, P. Schwarz, M. Holers, M. and Solomon, J. Doyle, T. Debray, M. -P. Boileau, C. and Crestani, B. Schwartz, D. Dieude, P.

Published
2018

21. Modulation of methotrexate-induced intestinal mucosal injury by dietary factors.

Author

Higuchi, T, Yoshimura, M, Oka, S, Tanaka, K, Naito, T, Yuhara, S, Warabi, E, Mizuno, S, Ono, M, Takahashi, S, Tohma, S, Tsuchiya, N, and Furukawa, H

Subjects
INTESTINAL injuries, HIGH-fat diet, FECAL analysis, PATHOLOGY, NEOMYCIN, INTESTINAL mucosa, SUCROSE, INTESTINAL physiology
Abstract

Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment. [ABSTRACT FROM AUTHOR]

Published
2020
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22. OP0284 Muc5b promoter variant rs35705950 is a risk factor for rheumatoid arthritis – interstitial lung disease

Author

Juge, P.-A., primary, Lee, J.S., additional, Ebstein, E., additional, Furukawa, H., additional, Dobrinskikh, E., additional, Gazal, S., additional, Kannengiesser, C., additional, Ottaviani, S., additional, Tsuchiya, N., additional, Oka, S., additional, Tohma, S., additional, Rojas-Serrano, J., additional, Gonzalez-Perez, M.-I., additional, Mejia, M., additional, Buendia-Roldan, I., additional, Falfan-Valencia, R., additional, Manali, E., additional, Papiris, S.A., additional, Karageorgas, T., additional, Boumpas, D., additional, Antoniou, K., additional, Van Moorsel, C., additional, van der Vis, J., additional, de Man, Y., additional, Grutters, J., additional, Wang, Y., additional, Borie, R., additional, Wemeau-Stervinou, L., additional, Wallaert, B., additional, Flipo, R.-M., additional, Nunes, H., additional, Valeyre, D., additional, Saidenberg, N., additional, Marchand-Adam, S., additional, Deane, K., additional, Walts, A., additional, Fingerlin, T., additional, Matteson, E., additional, Niewold, T., additional, Assayag, D., additional, Gross, A., additional, Wolters, P., additional, Schwarz, M., additional, Holers, M., additional, Solomon, J., additional, Doyle, T., additional, Debray, M.-P., additional, Boileau, C., additional, Crestani, B., additional, Schwartz, D., additional, and Dieudé, P., additional

Published
2018
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27. TRANS-ETHNIC META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES IDENTIFIES GSDMA AND PRDM1 AS SUSCEPTIBILITY GENES TO SYSTEMIC SCLEROSIS

Author

Terao, C., Kawaguchi, T., Dieude, P., Varga, J., Kuwana, M., Hudson, M., Kawaguchi, Y., Matucci-Cerinic, M., Ohmura, K., Riemekasten, G., Kawasaki, A., Airo, P., Horita, T., Oka, A., Hachulla, E., Yoshifuji, H., Caramaschi, P., Hunzelmann, N., Baron, M., Atsumi, T., Hassouns, P., Tochimoto, A., Ayuzawa, N., Yanagida, H., Furukawa, H., Tohma, S., Hasegawa, M., Fujimoto, M., Ishikawa, O., Yamamoto, T., Goto, D., Asano, Y., Jinnin, M., Endo, H., Takahashi, H., Takehara, K., Sato, S., Ihn, H., Raychaudhuri, S., Liao, K., Gregersen, P., Tsuchiya, N., Riccieri, V., Melchers, I., Valentini, G., Cauvet, A., Martinez, M., Mimori, T., Matsuda, F., Allanore, Y., Terao, C., Kawaguchi, T., Dieude, P., Varga, J., Kuwana, M., Hudson, M., Kawaguchi, Y., Matucci-Cerinic, M., Ohmura, K., Riemekasten, G., Kawasaki, A., Airo, P., Horita, T., Oka, A., Hachulla, E., Yoshifuji, H., Caramaschi, P., Hunzelmann, N., Baron, M., Atsumi, T., Hassouns, P., Tochimoto, A., Ayuzawa, N., Yanagida, H., Furukawa, H., Tohma, S., Hasegawa, M., Fujimoto, M., Ishikawa, O., Yamamoto, T., Goto, D., Asano, Y., Jinnin, M., Endo, H., Takahashi, H., Takehara, K., Sato, S., Ihn, H., Raychaudhuri, S., Liao, K., Gregersen, P., Tsuchiya, N., Riccieri, V., Melchers, I., Valentini, G., Cauvet, A., Martinez, M., Mimori, T., Matsuda, F., and Allanore, Y.

Published
2017

30. THU0710 Validation of new weighted scoring system to predict modified health assessment questionnaire scores in patients with rheumatoid arthritis using national database of rheumatic diseases in japan during 2009 and 2014

Author

Ono, K, primary, Ohashi, S, additional, Kadono, Y, additional, Oka, H, additional, Hirose, J, additional, Matsumoto, T, additional, Izawa, N, additional, Naito, M, additional, Nishino, J, additional, Tanaka, S, additional, and Tohma, S, additional

Published
2017
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31. THU0006 Trans-ethnic meta-analysis of genome-wide association studies identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis

Author

Terao, C, primary, Kawaguchi, T, additional, Dieude, P, additional, Varga, J, additional, Kuwana, M, additional, Hudson, M, additional, Kawaguchi, Y, additional, Matucci-Cerinic, M, additional, Ohmura, K, additional, Riemekasten, G, additional, Kawasaki, A, additional, Airo, P, additional, Horita, T, additional, Oka, A, additional, Hachulla, E, additional, Yoshifuji, H, additional, Caramaschi, P, additional, Hunzelmann, N, additional, Baron, M, additional, Atsumi, T, additional, Hassouns, P, additional, Tochimoto, A, additional, Ayuzawa, N, additional, Yanagida, H, additional, Furukawa, H, additional, Tohma, S, additional, Hasegawa, M, additional, Fujimoto, M, additional, Ishikawa, O, additional, Yamamoto, T, additional, Goto, D, additional, Asano, Y, additional, Jinnin, M, additional, Endo, H, additional, Takahashi, H, additional, Takehara, K, additional, Sato, S, additional, Ihn, H, additional, Raychaudhuri, S, additional, Liao, K, additional, Gregersen, P, additional, Tsuchiya, N, additional, Riccieri, V, additional, Melchers, I, additional, Valentini, G, additional, Cauvet, A, additional, Martinez, M, additional, Mimori, T, additional, Matsuda, F, additional, and Allanore, Y, additional

Published
2017
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34. AB1058 The New Joint Weighted Scoring System Which Predicts The Modified Health Assessment Questionnaires Scores in Rheumatoid Arthritis Patients: A Validation Study Using The National Database of Rheumatic Diseases by iR-net in Japan

Author

Ono, K., primary, Ohashi, S., additional, Oka, H., additional, Kadono, Y., additional, Omata, Y., additional, Matsumoto, T., additional, Izawa, N., additional, Nishino, J., additional, Tanaka, S., additional, and Tohma, S., additional

Published
2016
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38. AB0365 Prevalence and Factors Associated with Depression and Anxiety in Patients with Rheumatoid Arthritis Using Data from a Large Japanese Cohort Database in 2013 (Ninja 2013 Database)

Author

Katayama, M., primary, Miyamura, T., additional, Suenaga, Y., additional, Suematsu, E., additional, Urata, Y., additional, Matsui, T., additional, Kaneko, A., additional, Kida, D., additional, Sato, T., additional, Kawabe, Y., additional, Yoshizawa, S., additional, Tsunoda, S., additional, Sano, H., additional, Saisho, K., additional, Takahi, K., additional, Nishino, J., additional, and Tohma, S., additional

Published
2015
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39. SAT0120 Ninja, A Japanese Rheumatoid Arthritis Database, Demonstrated that the Size and Number of Swollen Joints Correlated with Increased Systemic Inflammation Markers. Digital Joint Swelling Showed Only Trace Increases of Serum C-Reactive Protein and Erythrocyte Sedimentation Rate

Author

Shimada, K., primary, Komiya, A., additional, Onishi, K., additional, Kise, T., additional, Miyoshi, Y., additional, Nagai, Y., additional, Kikuchi, E., additional, Nunokawa, T., additional, Sawaki, T., additional, Yokogawa, N., additional, Sugii, S., additional, and Tohma, S., additional

Published
2015
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42. SAT0074 Smoking Cessation Significantly Reduces Failure of BIOLOGICS (BIO)-Treatment in Rheumatoid Arthritis (RA): from the “Ninja” Registry Cohort of Japanese Patients

Author

Saeki, Y., primary, Matsui, T., additional, Kagawa, K., additional, Ohshima, S., additional, Matsushita, M., additional, Tanaka-Kudo, E., additional, Tsuji, S.-I., additional, Yoshimura, M., additional, Watanabe, A., additional, Teshigawara, S., additional, Katayama, M., additional, Katada, Y., additional, Harada, Y., additional, Yura, A., additional, Hashimoto, J., additional, and Tohma, S., additional

Published
2014
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43. THU0567 Using the National Database of Rheumatic Diseases by Ir-Net in Japan to Investigate Factors Influencing Medium-Term Physical Function following Total Knee and Total Hip Arthroplasty

Author

Ohashi, S., primary, Kadono, Y., additional, Yasui, T., additional, Ono, K., additional, Oka, H., additional, Nishino, J., additional, Tanaka, S., additional, Mori, T., additional, Masuda, K., additional, Iwasawa, M., additional, Matsui, T., additional, and Tohma, S., additional

Published
2014
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44. THU0179 Cross-National Comparison of Biological Disease-Modifying Antirheumatic Drug Discontinuation Practice among Rheumatoid Arthritis Patients in Remission: Corrona and Ninja Collaboration

Author

Yoshida, K., primary, Radner, H., additional, Mjaavatten, M.D., additional, Greenberg, J.D., additional, Kavanaugh, A., additional, Kishimoto, M., additional, Matsui, K., additional, Okada, M., additional, Reed, G., additional, Saeki, Y., additional, Tohma, S., additional, Kremer, J., additional, and Solomon, D.H., additional

Published
2014
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45. THU0562 The Impacts of Disease of the Joints on Modified Health Assessment Questionnaire Scores in Rheumatoid Arthritis Patients: A Retrospective Study Using the National Database of Rheumatic Diseases by Ir-Net in Japan

Author

Ono, K., primary, Ohashi, S., additional, Oka, H., additional, Kadono, Y., additional, Yasui, T., additional, Isawa, K., additional, Shoda, N., additional, Nishino, J., additional, Tanaka, S., additional, and Tohma, S., additional

Published
2014
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46. Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope.

Author

Goldberg, AC, Furukawa, H, Oka, S, Shimada, K, Sugii, S, Ohashi, J, Matsui, T, Ikenaka, T, Nakayama, H, Hashimoto, A, Takaoka, H, Arinuma, Y, Okazaki, Y, Futami, H, Komiya, A, Fukui, N, Nakamura, T, Migita, K, Suda, A, Nagaoka, S, Tsuchiya, N, Tohma, S, Goldberg, AC, Furukawa, H, Oka, S, Shimada, K, Sugii, S, Ohashi, J, Matsui, T, Ikenaka, T, Nakayama, H, Hashimoto, A, Takaoka, H, Arinuma, Y, Okazaki, Y, Futami, H, Komiya, A, Fukui, N, Nakamura, T, Migita, K, Suda, A, Nagaoka, S, Tsuchiya, N, and Tohma, S

Abstract

INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. METHODS: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA.

Published
2012

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