A Patel1,2, S Hasak2, B D Nix2, G S Sayuk2, R D Newberry2, C P Gyawali2. 1. Duke University School of Medicine, Durham VA Medical Center, Durham, NC, USA. 2. Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA.
Abstract
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.
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.
Authors: V M Kushnir; A Sathyamurthy; J Drapekin; S Gaddam; G S Sayuk; C P Gyawali Journal: Aliment Pharmacol Ther Date: 2012-03-20 Impact factor: 8.171
Authors: V M Kushnir; B Cassell; C P Gyawali; R D Newberry; P Kibe; B D Nix; A Sabzpoushan; N D Kanuri; G S Sayuk Journal: Aliment Pharmacol Ther Date: 2013-06-20 Impact factor: 8.171