RGD Reference Report - Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia. - Rat Genome Database

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

Authors: Mujakovic, S  Ter Linde, JJ  De Wit, NJ  Van Marrewijk, CJ  Fransen, GA  Onland-Moret, NC  Laheij, RJ  Muris, JW  Grobbee, DE  Samsom, M  Jansen, JB  Knottnerus, A  Numans, ME 
Citation: Mujakovic S, etal., BMC Med Genet. 2011 Oct 20;12:140. doi: 10.1186/1471-2350-12-140.
RGD ID: 6480658
Pubmed: PMID:22014438   (View Abstract at PubMed)
PMCID: PMC3213216   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2350-12-140   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR3AHumanDyspepsia  IAGP DNA:SNP:promoter:c.-42C>T(human)RGD 
Htr3aMouseDyspepsia  ISOHTR3A (Homo sapiens)DNA:SNP:promoter:c.-42C>T(human)RGD 
Htr3aRatDyspepsia  ISOHTR3A (Homo sapiens)DNA:SNP:promoter:c.-42C>T(human)RGD 
SLC6A4HumanDyspepsia  IAGP DNA:polymorphism: :RGD 
Slc6a4RatDyspepsia  ISOSLC6A4 (Homo sapiens)DNA:polymorphism: :RGD 
Slc6a4MouseDyspepsia  ISOSLC6A4 (Homo sapiens)DNA:polymorphism: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr3a  (5-hydroxytryptamine receptor 3A)
Slc6a4  (solute carrier family 6 member 4)

Genes (Mus musculus)
Htr3a  (5-hydroxytryptamine (serotonin) receptor 3A)
Slc6a4  (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)

Genes (Homo sapiens)
HTR3A  (5-hydroxytryptamine receptor 3A)
SLC6A4  (solute carrier family 6 member 4)


Additional Information