Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2017; 23(29): 5364-5370
Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5364
Genetic polymorphisms of MAFK, encoding a small Maf protein, are associated with susceptibility to ulcerative colitis in Japan
Tomiyasu Arisawa, Masakatsu Nakamura, Toshimi Otsuka, Wu Jing, Naoko Sakurai, Hikaru Takano, Tasuku Hayashi, Masafumi Ota, Tomoe Nomura, Ranji Hayashi, Takeo Shimasaki, Tomomitsu Tahara, Tomoyuki Shibata
Tomiyasu Arisawa, Masakatsu Nakamura, Toshimi Otsuka, Wu Jing, Naoko Sakurai, Hikaru Takano, Tasuku Hayashi, Masafumi Ota, Tomoe Nomura, Ranji Hayashi, Takeo Shimasaki, Department of Gastroenterology, Kanazawa Medical University, Ishikawa 920-0293, Japan
Tomomitsu Tahara, Tomoyuki Shibata, Department of Gastroenterology, Fujita Health University, Kutsukake-cho, Toyoake 470-1192, Japan
Author contributions: Arisawa T analyzed the data, wrote the paper and was responsible for the conception of the study and designed the study; Nakamura M, Otsuka T, Sakurai N, Takano H, Hayashi T, Ota M, Nomura T and Hayashi R obtained the samples and the data; Jing W and Shimasaki T determined genotype; Tahara T and Shibata T participated in the design of the study.
Institutional review board statement: The study was approved by the Ethics Committee of Kanazawa Medical University (Uchinada-machi, Japan) and Fujita Health University (Toyoake, Japan).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: There are no conflicts of interest.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at tarisawa@kanazawa-med.ac.jp. Informed consent form participants for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tomiyasu Arisawa, MD, PhD, Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan. tarisawa@kanazawa-med.ac.jp
Telephone: +81-76-2188154 Fax: +81-76-2860892
Received: January 24, 2017
Peer-review started: February 1, 2017
First decision: March 3, 2014
Revised: March 14, 2014
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: August 7, 2017
Processing time: 194 Days and 18.4 Hours
Abstract
AIM

To investigate whether single nucleotide polymorphisms in maf protein K (MAFK), which encodes the MAFK, lead to increased susceptibility to ulcerative colitis in the Japanese population.

METHODS

This case control study examined the associations between MAFK single nucleotide polymorphisms (rs4268033 G>A, rs3735656 T>C and rs10226620 C>T) and ulcerative colitis susceptibility in 174 patients with ulcerative colitis (UC) cases, and 748 subjects without no lower abdominal symptoms, diarrhea or hematochezia (controls). In addition, as the second controls, we set 360 subjects, who have an irregular bowel movement without abnormal lower endoscopic findings (IBM controls).

RESULTS

The genotype frequency of rs4268033 AA and allelic frequency of the rs4268033A allele were significantly higher in the UC cases than in both controls (P = 0.0005 and < 0.0001, P = 0.015 and 0.0027 vs controls and IBM controls, respectively). Logistic regression analysis after adjustment for age and gender showed that the rs4268033 AA and rs3735656 CC genotypes were significantly associated with susceptibility to UC development (OR = 2.63, 95%CI: 1.61-4.30, P = 0.0001 and OR = 1.81; 95%CI: 1.12-2.94, P = 0.015, respectively). Similar findings were observed by the comparison with IBM controls. In addition, the rs4268033 AA genotype was significantly associated with all phenotypes of UC except early onset. There was no significant association between rs10226620 and ulcerative colitis.

CONCLUSION

Our results provide the first evidence that MAFK genetic polymorphisms are significantly associated with susceptibility to UC development. In particular, rs4268033 is closely associated with an increased risk for the development of UC.

Keywords: Maf protein K; Genetic polymorphism; Reactive oxygen species; Ulcerative colitis; Nuclear factor-erythroid 2-related factor 2

Core tip: We investigated the association between maf protein K (MAFK), polymorphisms and ulcerative colitis in Japan. Both rs4268033 and rs3735656 minor allele homozygotes were significantly associated with the susceptibility to ulcerative colitis (UC) development. In addition, rs4268033 minor allele homozygote was significantly associated with all phenotypes of UC except the phenotype with younger age onset. Our results provided the first evidence that MAFK genetic polymorphisms were significantly associated with the susceptibility to UC development.