ABSTRACT
BACKGROUND: Genetic polymorphisms in G-protein beta-3 subunit (GNß3) 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 GNß3 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 GNß3 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 GNß3 predicts oesophageal symptom burden and affect, but not oesophageal acid burden or symptom association with reflux episodes.
Subject(s)
Food Hypersensitivity/genetics , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/genetics , Genetic Predisposition to Disease , Pain Perception , Pain/genetics , Adult , Aged , Case-Control Studies , Cohort Studies , Cost of Illness , Female , Food Hypersensitivity/complications , Food Hypersensitivity/epidemiology , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/epidemiology , Genotype , Heterotrimeric GTP-Binding Proteins/genetics , Humans , Male , Middle Aged , Pain/epidemiology , Pain/etiology , Pain Measurement , Pilot Projects , Polymorphism, Single Nucleotide , Receptors, Adrenergic, beta-2/genetics , Risk Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND: Sleep disturbances are common, and perhaps are even more prevalent in irritable bowel syndrome (IBS). AIMS: To determine the effect of measured sleep on IBS symptoms the following day, IBS-specific quality of life (IBS-QOL) and non-GI pain symptoms. METHODS: IBS patients' sleep patterns were compared to healthy individuals via wrist-mounted actigraphy over 7 days. Daily bowel pain logs (severity, distress; 10-point Likert) stool pattern (Bristol scale) and supporting symptoms (e.g. bloating, urgency; 5-point Likert) were kept. Validated measures, including the GI Symptom Rating Scale-IBS, Visceral Sensitivity Index, Pittsburgh Sleep Quality Index and the IBS-Quality of Life were collected. Mediation analysis explored the relationship between sleep, mood and bowel symptoms. RESULTS: Fifty subjects (38.6 ± 1.0 years old, 44 female; 24 IBS and 26 healthy controls) completed sleep monitoring. IBS patients slept more hours per day (7.7 ± 0.2 vs. 7.1 ± 0.1, P = 0.008), but felt less well-rested. IBS patients demonstrated more waking episodes during sleep (waking episodes; 12.1 vs. 9.3, P < 0.001). Waking episodes predicted worse abdominal pain (P ≤ 0.01) and GI distress (P < 0.001), but not bowel pattern or accessory IBS symptoms (P > 0.3 for each). Waking episodes negatively correlated with general- and IBS-specific QOL in IBS (r = -0.58 and -0.52, P < 0.001 for each). Disturbed sleep effects on abdominal pain were partially explained by mood as an intermediate. CONCLUSIONS: Sleep disturbances are more common in irritable bowel syndrome, and correlate with IBS-related pain, distress and poorer irritable bowel syndrome-related quality of life. Disturbed sleep effects extend beyond the bowel, leading to worse mood and greater somatic pain in patients with the irritable bowel syndrome.