Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Nov 6, 2017; 8(4): 193-200
Published online Nov 6, 2017. doi: 10.4292/wjgpt.v8.i4.193
Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn’s disease
Ioannis Papaconstantinou, Christina Kapizioni, Evangelia Legaki, Elena Xourgia, George Karamanolis, Antonios Gklavas, Maria Gazouli
Ioannis Papaconstantinou, Antonios Gklavas, 2nd Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
Christina Kapizioni, Gastroenterology Department, Tzaneion General Hospital, 18536 Piraeus, Greece
Evangelia Legaki, Elena Xourgia, Maria Gazouli, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
George Karamanolis, Gastroenterology Unit, 2nd Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
Author contributions: Papaconstantinou I, Kapizioni C, Karamanolis G and Gazouli M conceived and designed the study; Kapizioni C, Legaki E, Xourgia E, Gklavas A and Gazouli M acquired, analyzed, and interpreted data; Kapizioni C and Gazouli M wrote the original draft; Papaconstantinou I, Gazouli M and Karamanolis G reviewed, and approved the article.
Institutional review board statement: The study was reviewed and approved by the Aretaieio Hospital Institutional Review Board.
Informed consent statement: All study participants, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None to declare.
Data sharing statement: No additional data are available.
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: Maria Gazouli, Associate Professor, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece. mgazouli@med.uoa.gr
Telephone: +30-2107-462231 Fax: +30-2107-462231
Received: May 29, 2017
Peer-review started: June 8, 2017
First decision: August 8, 2017
Revised: August 21, 2017
Accepted: September 14, 2017
Article in press: September 15, 2017
Published online: November 6, 2017
Abstract
AIM

To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn’s disease (CD).

METHODS

One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR.

RESULTS

One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients’ characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.

CONCLUSION

No correlation is detected between studied polymorphisms and patients’ response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

Keywords: MicroRNA, Crohn’s disease, Polymorphisms, Anti-TNF, Biomarkers

Core tip: Anti-TNF agents are the cornerstone of inflammatory bowel disease (IBD) treatment strategy so far though not effective in one third of patients in the first months of administration. Biomarkers for prediction of each patient’s treatment response are vigorously sought in the era of personalized medicine. MicroRNAs have been studied as possible predictors of response to therapy in cancer and autoimmune diseases including IBD. MiRNA polymorphisms though have never been studied in IBD as markers of anti-TNF response. Our results suggest that for rs2910164, rs11614913, rs113054794, and rs188519172 no association to anti-TNF agents’ response in patients with Crohn’s disease can be established.