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World J Clin Cases. Aug 16, 2018; 6(8): 176-182
Published online Aug 16, 2018. doi: 10.12998/wjcc.v6.i8.176
Risk factors for gastroesophageal reflux disease and analysis of genetic contributors
Alexandra Argyrou, Evangelia Legaki, Christos Koutserimpas, Maria Gazouli, Ioannis Papaconstantinou, George Gkiokas, George Karamanolis
Alexandra Argyrou, Evangelia Legaki, Maria Gazouli, Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
Christos Koutserimpas, 2nd Department of General Surgery, “Sismanoglion” General Hospital of Athens, Athens 11527, Greece
Ioannis Papaconstantinou, George Gkiokas, 2nd Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
George Karamanolis, Gastroenterology Unit, 2nd Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No conflicts of interest.
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, PhD, Associate Professor, Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, Athens 11527, Greece. mgazouli@med.uoa.gr
Telephone: +30-210-7462231
Received: May 3, 2018
Peer-review started: May 4, 2018
First decision: May 22, 2018
Revised: May 31, 2018
Accepted: June 8, 2018
Article in press: June 8, 2018
Published online: August 16, 2018
Abstract

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett’s esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett’s esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

Keywords: Single nucleotide polymorphisms, Genetic risk loci, Risk factors, Gastroesophageal reflux disease, Gastroesophageal reflux disease development

Core tip: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder, which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years. Motor esophageal and gastric abnormalities, along with anatomical factors could contribute to GERD development. Genetic contributors seem to play a major role in GERD. Numerous single-nucleotide polymorphisms in various genetic loci have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.