Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2015; 21(36): 10358-10366
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10358
TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development
Natalia Volodko, Mohamed Salla, Bertus Eksteen, Richard N Fedorak, Hien Q Huynh, Shairaz Baksh
Natalia Volodko, Hien Q Huynh, Shairaz Baksh, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
Mohamed Salla, Shairaz Baksh, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
Bertus Eksteen, Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, AB T2N 1N4, Canada
Richard N Fedorak, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
Shairaz Baksh, Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
Author contributions: Volodko N and Salla M contributed equally to this work; Volodko N and Salla M performed the research; Volodko N, Salla M and Baksh S analyzed the data and wrote the manuscript; Eksteen B, Fedorak RN and Huynh HQ provided patient samples.
Supported by Grants from AI-HS and The Stollery Children’s Foundation/Hair Massacure Grant (under the Department of Pediatric generously donated by the MacDonald family; to Baksh S); Queen Elizabeth II Graduate Scholarship, the Biochemistry Doctoral Recruitment Scholarship and The Stollery Children’s Foundation/Hair Massacure Grant (to Salla M).
Institutional review board statement: The study was approved by the human Ethics Research Board under the protocol No. Pro00001523 (study No. RES1598); and informed consent was obtained from all patients and controls before samples were analyzed.
Conflict-of-interest statement: The authors declare no conflict of interest with respect to competing commercial, personal, political, intellectual, or religious interests in relation to the submitted work.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at sbaksh@ualberta.ca. Participants gave informed consent for data sharing.
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: Dr. Shairaz Baksh, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3020E Katz Research Building, 113 St. 87 Ave., Edmonton, AB T6G 2E1, Canada. sbaksh@ualberta.ca
Telephone: +1-780-4920723 Fax: +1-780-4923494
Received: February 25, 2015
Peer-review started: February 26, 2015
First decision: March 26, 2015
Revised: April 28, 2015
Accepted: July 15, 2015
Article in press: July 15, 2015
Published online: September 28, 2015
Abstract

AIM: To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development.

METHODS: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood.

RESULTS: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients.

CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.

Keywords: Inflammatory bowel disease, Colorectal cancer, 72 codon single nucleotide polymorphism, Tumor protein 53, rs1042522

Core tip: Tumor protein 53 (TP53) codon 72 polymorphism distribution was analyzed by RFLP in 461 inflammatory bowel disease (IBD), 181 primary sclerosing cholangitis patents and in 62 healthy controls. The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.