Genetic risk factors for perception of symptoms in GERD: an observational cohort study

• Published in: Alimentary pharmacology & therapeutics Vol. 47; no. 2; pp. 289 - 297
• Main Authors: Patel, A., Hasak, S., Nix, B. D., Sayuk, G. S., Newberry, R. D., Gyawali, C. P.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2018
• Subjects: Adrenergic receptors; Adult; Aged; Anxiety; Case-Control Studies; Cohort analysis; Cohort Studies; Cost of Illness; Esophagus; Female; Food Hypersensitivity - complications; Food Hypersensitivity - epidemiology; Food Hypersensitivity - genetics; Foregut; Gastroesophageal reflux; Gastroesophageal Reflux - complications; Gastroesophageal Reflux - diagnosis; Gastroesophageal Reflux - epidemiology; Gastroesophageal Reflux - genetics; Genetic diversity; Genetic Predisposition to Disease; Genotype; Genotyping; Heterotrimeric GTP-Binding Proteins - genetics; Humans; Hypersensitivity; Male; Mental disorders; Middle Aged; Movement disorders; Observational studies; Pain; Pain - epidemiology; Pain - etiology; Pain - genetics; Pain Measurement; Pain Perception; Pilot Projects; Polymorphism, Single Nucleotide; Quality of life; Receptors, Adrenergic, beta-2 - genetics; Risk Factors; Saliva; Single-nucleotide polymorphism; Surgery; Surveys and Questionnaires
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.14414

Summary Background Genetic polymorphisms in G‐protein beta‐3 subunit (GNβ3) and beta‐2 adrenergic receptor (ADRB2) are associated with pain and gut hypersensitivity, which can overlap with gastroesophageal reflux disease (GERD). Aim To evaluate relationships between single nucleotide polymorphisms (SNPs) within GNβ3 and ADRB2 systems, and reflux symptom burden, GERD phenotypes from ambulatory reflux monitoring, and quality of life. Methods Symptomatic adults undergoing ambulatory reflux testing were recruited and phenotyped based on acid burden and symptom reflux association; major oesophageal motor disorders and prior foregut surgery were exclusions. A comparison asymptomatic control cohort was also identified. Subjects and controls completed questionnaires assessing symptom burden on visual analog scales, short‐form health survey‐36 (SF‐36), and Beck Anxiety and Depression Inventories (BAI and BDI). Genotyping was performed from saliva samples; 6 SNPs selected from each of the two genes of interest were compared. Results Saliva from 151 study subjects (55.3 ± 1.2 years, 63.6% F) and 60 control subjects (50.9 ± 2.2 years, 66.7%) had sufficient genetic material for genotyping. Study subjects had higher symptom burden, worse total and physical health, and higher anxiety scores compared to controls (P ≤ .002). Tested SNPs within ADRB2 were similar between study subjects and controls (P > .09). Study subjects with recessive alleles in 3 GNβ3 SNPs (Rs2301339, Rs5443, and Rs5446) had worse symptom severity (P = .011), worse mental health (P = .03), and higher depression scores (P = .005) despite no associations with GERD phenotypes or reflux metrics. Conclusions Genetic variation within GNβ3 predicts oesophageal symptom burden and affect, but not oesophageal acid burden or symptom association with reflux episodes.