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.

Opioid medication use in patients with gastrointestinal diagnoses vs unexplained gastrointestinal symptoms in the US Veterans Health Administration.

BACKGROUND: While opioid prescriptions have increased alarmingly in the United States (US), their use for unexplained chronic gastrointestinal (GI) pain (eg, irritable bowel syndrome) carries an especially high risk for adverse effects and questionable benefit. AIM: To compare opioid use among US veterans with structural GI diagnoses (SGID) and those with unexplained GI symptoms or functional GI diagnoses (FGID), a group for whom opioids have no accepted role. METHODS: Veterans Health Administration (VHA) administrative data from fiscal year 2012 were used to identify veterans with diagnostic codes recorded for SGID and FGID. This cohort study examined VHA pharmacy data to compare groups receiving ≥ 1 opioid prescription during the year and number of prescriptions filled. Bivariate and multiple logistic regression analyses adjusted for potential confounding factors (demographics, medical diagnoses, social factors) and identified potential mediators (service use, psychiatric comorbidity) of opioid use in these groups. RESULTS: A greater proportion of veterans with FGID received an opioid prescription during fiscal year 2012 (36.0% of 272 431) compared to only 28.9% of 1 223 744 in the SGID group (Relative Risk [RR] = 1.25). In multivariate logistic regression, personality disorders and drug abuse (OR 1.23 for each group), recent homelessness (OR 1.22), psychotropic medication fills (OR 1.55) and emergency department encounters (OR 1.21) were independently associated with opioid prescription use. CONCLUSIONS: Despite the potential for adverse consequences, opioids more often are prescribed for veterans with chronic, unexplained GI symptoms compared to those with structural diagnoses. Psychiatric comorbidities and frequent healthcare encounters mediate some of the opioid use risk.

Genetic variation in the beta-2 adrenergic receptor (ADRB2) predicts functional gastrointestinal diagnoses and poorer health-related quality of life.

BACKGROUND: The beta-2 adrenergic receptor (ADRB2) is an important target for epinephrine, a neurotransmitter in pain signalling. ADRB2 haplotypes affect receptor expression and ligand response, and have been linked to painful non-GI disorders. AIMS: To assess whether ADRB2 polymorphisms (rs1042713, rs1042714) are risk alleles for functional GI (FGID) and extraintestinal functional (EIFD) diagnoses, and whether ADRB2 predicts GI symptoms and health-related quality of life (HRQOL). METHODS: Of 398 subjects (49.6 ± 2.9 years, 68.0% female), 170 (42.5%) met Rome III criteria for ≥1 FGID [IBS (n = 139, 34.9%); functional dyspepsia (FD, n = 136, 34.1%), functional chest pain (FCP, n = 25, 6.2%)], while 228 were healthy controls. FGID subjects reported on bowel symptom severity and burden (10-cm VAS), frequency (days/last 2 weeks), EIFD, psychiatric diagnoses and HRQOL (SF 36). Multivariable models determined the contribution of ADRB2 polymorphisms to HRQOL, and mediational analyses assessed functional diagnoses as potential intermediates. RESULTS: rs1042714 minor G alleles were associated with FGID diagnoses (OR 1.8; 95% CI 1.2-2.7; P = 0.009), particularly FD (OR 2.1, 95% CI 1.3-3.3), with trends towards IBS (P = 0.19) and FCP (P = 0.06) diagnoses. Within IBS, G allele carriers had more severe bowel symptoms (P = 0.025), and symptomatic days (P = 0.009). G allele carriers had greater numbers of EIFD (1.0 ± 0.1 vs. 0.4 ± 0.07, P < 0.001) and poorer HRQOL. The effect of ADRB2 on HRQOL was partially mediated by FGID, EIFD and psychiatric diagnoses. CONCLUSIONS: ADRB2 minor alleles at rs1042714 predict FGID and EIFD, and may influence bowel symptom severity and HRQOL. These findings provide indirect evidence of sympathetic nervous system role in FGID pathophysiology.