ArticleBMC medical genetics2011
Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.
Article in BMC medical genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- The serotonin receptor 3E variant is a risk factor for female IBS-D.Journal of molecular medicine (Berlin, Germany) · 2022Pooled it
- Guideline
- Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.The American journal of gastroenterology · 2017Trial
- Tapping into 5-HTInternational journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Immunopathological and molecular basis of functional dyspepsia and current therapeutic approaches.Expert review of clinical immunology · 2018Review
- Role of Gut Microbiota-Gut Hormone Axis in the Pathophysiology of Functional Gastrointestinal Disorders.Journal of neurogastroenterology and motility · 2018Review
- Gene polymorphisms associated with functional dyspepsia.World journal of gastroenterology · 2015Review
- Advances in Medications and Tailoring Treatment for Alcohol Use Disorder.Alcohol research : current reviews · 2015Review
- Genetic polymorphism in pathogenesis of irritable bowel syndrome.World journal of gastroenterology · 2014Review
- Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists?Current oncology reports · 2013Review
- Duodenal epithelial transport in functional dyspepsia: Role of serotonin.World journal of gastrointestinal pathophysiology · 2013Article
- Overlap of functional dyspepsia and GERD--diagnostic and treatment implications.Nature reviews. Gastroenterology & hepatology · 2013Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsData 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.
resultsHTR3A 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).
conclusionsThe 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.
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