Argyrou Alexandra, Legaki Evangelia, Koutserimpas Christos, Gazouli Maria, Papaconstantinou Ioannis, Gkiokas George, Karamanolis George
Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece.
2 Department of General Surgery, "Sismanoglion" General Hospital of Athens, Athens 11527, Greece.
World J Clin Cases. 2018 Aug 16;6(8):176-182. doi: 10.12998/wjcc.v6.i8.176.
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 , , , 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.
胃食管反流病（GERD）是一种常见的胃肠道疾病，其患病率呈上升趋势。当胃内容物反流导致出现令人困扰的典型和非典型症状及/或并发症时，就会发生胃食管反流病。多年来，已经确定并评估了胃食管反流病的多种危险因素，其中包括相当数量的遗传因素。胃食管反流病的发病机制涉及多种机制，包括：（1）运动异常，如下食管括约肌（LES）静息张力受损、LES短暂松弛、食管酸清除受损和胃排空延迟；（2）解剖学因素，如食管裂孔疝和肥胖。遗传因素似乎在胃食管反流病以及与胃食管反流病相关的疾病（如巴雷特食管和食管腺癌）的发生发展中起主要作用。双胞胎和家族研究显示，该病的遗传度约为31%。多种基因（如 、 、 、抗炎细胞因子和DNA修复基因）中的众多单核苷酸多态性与胃食管反流病风险增加密切相关。胃食管反流病、巴雷特食管和食管腺癌有几个共同的基因位点。尽管胃食管反流病具有多基因基础，但特定的基因位点，如19号染色体上的rs10419226、3号染色体上的rs2687201、15号染色体上的rs10852151以及配对相关同源盒1基因上的rs520525，已被提及为潜在的危险因素。对风险基因的进一步研究可能会阐明它们的确切功能和作用，并为这种日益常见的疾病展示新的治疗方法。
