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

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.

Effects of disturbed sleep on gastrointestinal and somatic pain symptoms in irritable bowel syndrome.

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.