[page 4] [Gastroenterology Insights 2018; 9:7471] Role of human leukocyte antigens DRB1-DQB1 haplotype in the susceptibility to gastroesophageal reflux disease Batool Mutar Mahdi, 1 Riyadh Mohamad Hasan, 2 Wafaa Hazim 1 1 Department of Microbiology; 2 Department of Surgery, Al-Kindy College of Medicine, University of Baghdad, Iraq Abstract Gastro oesophageal reflux disease is due to involuntary gastric contents reflux into the esophagus from stomach, causing heartburn and acid regurgitation symptoms. Genetic and environmental factors are important factors in the causation of dis- ease. Human Leukocyte antigens consid- ered as an excellent marker for population genetics analysis and disease association. This study aimed to investigate the associa- tion between HLA-DRB1-DQB1 haplotype that inherited in linkage and its association with gastro oesophageal reflux disease (GERD). Patients and healthy controls were prospectively recruited from gastrocolono- scope unit at Al-Kindy Teaching Hospital (Baghdad-Iraq) between January and July 2016. Forty Iraqi Arab Muslims patients with a history of heartburn and dyspepsia compared with 100 Iraqi Arab Muslims control. All study patients and control group underwent upper gastroesophageal endo- scope examination and HLA-DRB1 and HLA-DQB1 genotype were done using sequence spesific oligonucleotide primer to both groups. The frequencies of two haplo- type HLA-DRB1/03-DQB1/03 and HLA- DRB1/13-DQB1/06 were significantly high- er in patients with GERD while haplotype HLA-DRB1/03-DQB1/02 was significantly higher in control group. Sex had an effect in disease developing that haplotype HLA- DRB1/03-DQB1/03 was significantly more common in female patients that increased susceptibility to disease. This study identi- fied that two haplotypes HLA-DRB1/03- DQB1/03 and HLA-DRB1/13- DQB1/06 leads to increased susceptibility to GERD and haplotype HLA-DRB1/03-DQB1/02 was protective against GERD development. Introduction According to Genval workshop in 1999 that defined gastroesophageal reflux dis- easeas (GERD) a disorder in the stomach which it’s contents recurrently reflux into the lower part of the oesophagus causing heartburn and other symptoms. 1 About one third of GERD patients had positive find- ings endoscopically and the rest had no obvious mucosal lesions. 2,3 The complica- tions of GERD are Barrett’s metaplasia that develops as a reaction to chronic damage by gastro-oesophageal reflux 4 and oesophageal adenocarcinoma. 5 The development of these complications was due to altered immune outline in response to different stimulations of different antigens that mod- ulate disease. 6 The cytotoxic T lymphocyte and T helper cells can recognize these anti- gens presented by HLA (human leukocyte antigen) HLA-class I or HLA-class II mol- ecules, respectively which plays an impor- tant role in immune response regulation. 7 One study found that there is an association between HLA-DRB1 *15:01 and GERD in patients with H. pylori positive infection. 8 Other study demonstrated that HLA B7 may increased susceptibility for Barrett’s oesophagus. 9 HLA-DR expression is found in the oesophageal tissue of patients with ongoing inflammation in the lamina propria and submucosa of the oesophageal as a result of cytokine release. 10 The advantages of HLA class II expression on some tumor cells appears to restrict tumor growth and increased survival through stimulation of CD4 T helper cell response against tumor. 11 This study aimed to investigate the association between HLA-DRB1-DQB1 haplotype that inherited in linkage and its association with gastro oesophageal reflux disease. Materials and Methods Patients with dyspepsia and heartburn and healthy controls were prospectively recruited from gastrocolonoscope unit at Al-Kindy Teaching Hospital in Baghdad- Iraq for the period between January and July 2016. The demographic details of all patients and control groups were recorded. Written informed consent was obtained from all patients and control group for this study. The study protocol was reviewed and approved by the Scientific and Ethical Committee of Al-Kindy medical college and Al-Kindy Teaching Hospital. The patient group and control groups were sex and age matched. Forty Iraqi Arab Muslims patients with a history of heartburn and dyspepsia had been referred for upper gastrointestinal endoscopy at GIT center at Al-Kindy Teaching Hospital, Baghdad and a diagno- sis of GERD were prospectively recruited. Those patients were compared with 100 Iraqi Arab Muslims control. All study patients and control group underwent upper gastroesophageal endoscope examination and HLA-DRB1 and HLA-DQB1 genotype were done using sequence spesific oligonu- cleotide primer to both groups. Patients with Barrett’s esophagus, esophageal varices, patients with secondary causes of gastro-oesophageal reflux dis- ease, patients who had consumed antacids, H2 blockers, proton pump inhibitors, non- steroidal anti-inflammatory drugs, alcohol, history of Helicobacter pylori eradication, subjects with a history of gastrointestinal surgery, peptic ulcer, and gastric cancer or with systemic disease requiring chronic medication were excluded from the study. The control group was include 100 Iraqi Arab Muslims individuals undergoing upper gastrointestinal endoscopy for rea- sons other than reflux symptoms, Barrett’s esophagus or any form of dyspepsia and heartburn. This group included those with normal OGD. Oesophagogastric examinations Both patients and control groups were Gastroenterology Insights 2018; volume 9:7471 Correspondence: Batool Mutar Mahdi, Department of Microbiology, Al-Kindy College of Medicine, University of Baghdad, Al-Nahda Square, Baghdad, Iraq. Tel.: 00.964.1.077.02.553215. E-mail: abas_susan@yahoo.com Key words: Haplotypes; HLA; Gastro oesophageal reflux disease. Contributions: BMM conducted the tests; RMH conducted the gastroscope exam; WH collected the data. Conflict of interest: the authors declare no potential conflict of interest. Funding: none. Received for publication: 29 October 2017. Accepted for publication: 28 December2017. This work is licensed under a Creative Commons Attribution NonCommercial 4.0 License (CC BY-NC 4.0). ©Copyright B.M. Mahdi et al., 2018 Licensee PAGEPress, Italy Gastroenterology Insights 2018; 9:7471 doi:10.4081/gi.2018.7471 Non-commercial use only