Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.

BACKGROUND: The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. METHODS: Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia. RESULTS: HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90). CONCLUSIONS: The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

Open access capture of patients with gastroesophageal reflux disease using an online patient-reported outcomes instrument.

BACKGROUND: Persons with gastroesophageal reflux disease (GERD) frequently search online for information about causes and treatment options. The GerdQ self-assessment questionnaire can be used for diagnosis of GERD and follow-up of symptoms. OBJECTIVES: To assess whether it is feasible (1) to study the prevalence and impact of GERD in persons visiting a GERD information website, and (2) to identify partial responsiveness to proton pump inhibitor (PPI) therapy using the GerdQ. METHODS: All visitors (aged 18-79 years) to a GERD information website between November 2008 and May 2011 were invited to complete the GerdQ online. The GerdQ questionnaire consists of 6 questions (score per question: 0-3). In respondents who did not use PPIs, we used the questionnaire to identify those with GERD (total score ≥8) and assess the influence of these symptoms on their daily life, divided into low (total score <3 on impact questions) and high impact (total score ≥3 on impact questions). In PPI users, we used the GerdQ to quantify partial responsiveness by any report of heartburn, regurgitation, sleep disturbance, or over-the-counter medication use for more than 1 day in the preceding week. We subsequently asked GerdQ respondents scoring ≥8 to complete the disease-specific Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. RESULTS: A total of 131,286 visitors completed the GerdQ, of whom 80.23% (n = 105,329) did not use a PPI. Of these, we identified 67,379 respondents (63.97%) to have GERD (n = 32,935; 48.88% high impact). We invited 14,028 non-PPI users to complete the QOLRAD questionnaire, of whom 1231 (8.78%) completed the questionnaire. Mean total QOLRAD scores were 5.14 (SEM 0.04) for those with high-impact GERD and 5.77 (SEM 0.04) for those with low-impact GERD (P < .001). In PPI users, 22,826 of 25,957 respondents (87.94%) reported partial responsiveness. We invited 6238 PPI users to complete the QOLRAD questionnaire, of whom 599 (9.60%) completed the disease-specific quality-of-life questionnaire. Mean total QOLRAD scores were 4.62 (SEM 0.05) for partial responders and 5.88 (SEM 0.14) for adequate responders (P < .001). CONCLUSIONS: The GerdQ identified GERD in many website respondents and measured partial responsiveness in the majority of PPI users. Both non-PPI users with GERD and PPI users with partial responsiveness were associated with a decreased health-related quality of life. We have shown the feasibility of GERD patient identification online.