Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan

Yoshihiro Miyake; Keiko Tanaka; Chisato Nagata; Shinya Furukawa; Akira Andoh; Tetsuji Yokoyama; Naoki Yoshimura; Kenichiro Mori; Tomoyuki Ninomiya; Yasunori Yamamoto; Eiji Takeshita; Yoshio Ikeda; Mitsuru Saito; Katsuhisa Ohashi; Hirotsugu Imaeda; Kazuki Kakimoto; Kazuhide Higuchi; Hiroaki Nunoi; Yuji Mizukami; Seiyuu Suzuki; Sakiko Hiraoka; Hiroyuki Okada; Keitarou Kawasaki; Masaaki Higashiyama; Ryota Hokari; Hiromasa Miura; Teruki Miyake; Teru Kumagi; Hiromasa Kato; Naohito Hato; Koji Sayama; Yoichi Hiasa; Japan Ulcerative Colitis Study Group

doi:10.1016/j.cyto.2024.156743

Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan

Cytokine. 2024 Nov:183:156743. doi: 10.1016/j.cyto.2024.156743. Epub 2024 Aug 30.

Authors

Yoshihiro Miyake¹, Keiko Tanaka², Chisato Nagata³, Shinya Furukawa⁴, Akira Andoh⁵, Tetsuji Yokoyama⁶, Naoki Yoshimura⁷, Kenichiro Mori⁸, Tomoyuki Ninomiya⁸, Yasunori Yamamoto⁹, Eiji Takeshita¹⁰, Yoshio Ikeda⁹, Mitsuru Saito¹¹, Katsuhisa Ohashi¹², Hirotsugu Imaeda⁵, Kazuki Kakimoto¹³, Kazuhide Higuchi¹³, Hiroaki Nunoi¹⁴, Yuji Mizukami¹⁵, Seiyuu Suzuki¹⁶, Sakiko Hiraoka¹⁷, Hiroyuki Okada¹⁷, Keitarou Kawasaki¹⁸, Masaaki Higashiyama¹⁹, Ryota Hokari¹⁹, Hiromasa Miura²⁰, Teruki Miyake²¹, Teru Kumagi²², Hiromasa Kato²³, Naohito Hato²⁴, Koji Sayama²⁵, Yoichi Hiasa²¹; Japan Ulcerative Colitis Study Group

Affiliations

¹ Department of Epidemiology and Public Health, Ehime University Graduate School of Medicine, Ehime, Japan. Electronic address: miyake.yoshihiro.ls@ehime-u.ac.jp.
² Department of Epidemiology and Public Health, Ehime University Graduate School of Medicine, Ehime, Japan.
³ Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
⁴ Health Services Center, Ehime University, Ehime, Japan.
⁵ Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
⁶ Department of Health Promotion, National Institute of Public Health, Saitama, Japan.
⁷ Ohori IBD Clinic, Tokyo, Japan.
⁸ Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.
⁹ Endoscopy Center, Ehime University Hospital, Ehime, Japan.
¹⁰ Center for Inflammatory Bowel Diseases, Ehime University Hospital, Ehime, Japan.
¹¹ Department of Gastroenterology, Tokuyama Central Hospital, Yamaguchi, Japan.
¹² Ohashi Clinic Participate in Gastro-Enterology and Ano-Proctology, Ehime, Japan.
¹³ Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
¹⁴ Kato Internal Medicine, Ehime, Japan.
¹⁵ Department of Gastroenterology, Matsuyama Shimin Hospital, Ehime, Japan.
¹⁶ Sumitomo Besshi Hospital, Ehime, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
¹⁸ Department of Internal Medicine and Gastroenterology, Saiseikai Imabari Hospital, Ehime, Japan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
²⁰ Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
²¹ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
²² Postgraduate Clinical Training Center, Ehime University Hospital, Ehime, Japan.
²³ Kato Dental Clinic, Ehime, Japan.
²⁴ Department of Otolaryngology, Head and Neck Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
²⁵ Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

PMID: 39213891
DOI: 10.1016/j.cyto.2024.156743

Abstract

Background: Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population.

Methods: The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking.

Results: The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44-0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype.

Conclusion: IL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.

Keywords: Gene–environment interaction; IL23R polymorphism; Japanese; Smoking; Ulcerative colitis.

MeSH terms

Adult
Aged
Case-Control Studies
Colitis, Ulcerative* / genetics
Female
Genetic Predisposition to Disease* / genetics
Genotype
Humans
Japan / epidemiology
Male
Middle Aged
Polymorphism, Single Nucleotide* / genetics
Receptors, Interleukin* / genetics
Smoking* / genetics

Substances

IL23R protein, human
Receptors, Interleukin