Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-10-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/12/140 |
| _version_ | 1830231875563552768 |
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| author | Grobbee Diederick E Muris Jean WM Laheij Robert JF Onland-Moret N Charlotte Fransen Gerdine AJ van Marrewijk Corine J de Wit Niek J ter Linde José JM Mujakovic Suhreta Samsom Melvin Jansen Jan BMJ Knottnerus André Numans Mattijs E |
| author_facet | Grobbee Diederick E Muris Jean WM Laheij Robert JF Onland-Moret N Charlotte Fransen Gerdine AJ van Marrewijk Corine J de Wit Niek J ter Linde José JM Mujakovic Suhreta Samsom Melvin Jansen Jan BMJ Knottnerus André Numans Mattijs E |
| author_sort | Grobbee Diederick E |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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-HT<sub>3 </sub>receptors. Interestingly, a functional polymorphism in <it>HTR3A</it>, encoding the 5-HT<sub>3 </sub>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.</p> <p>Methods</p> <p>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 <it>HTR3A </it>c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the <it>5-HTT </it>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.</p> <p>Results</p> <p><it>HTR3A </it>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).</p> <p>Conclusions</p> <p>The <it>HTR3A </it>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-HT<sub>3 </sub>mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the <it>HTR3A </it>c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.</p> |
| first_indexed | 2024-12-18T11:24:28Z |
| format | Article |
| id | doaj.art-12c73509be704c34af3da87aa5e77381 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-18T11:24:28Z |
| publishDate | 2011-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-12c73509be704c34af3da87aa5e773812022-12-21T21:09:45ZengBMCBMC Medical Genetics1471-23502011-10-0112114010.1186/1471-2350-12-140Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsiaGrobbee Diederick EMuris Jean WMLaheij Robert JFOnland-Moret N CharlotteFransen Gerdine AJvan Marrewijk Corine Jde Wit Niek Jter Linde José JMMujakovic SuhretaSamsom MelvinJansen Jan BMJKnottnerus AndréNumans Mattijs E<p>Abstract</p> <p>Background</p> <p>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-HT<sub>3 </sub>receptors. Interestingly, a functional polymorphism in <it>HTR3A</it>, encoding the 5-HT<sub>3 </sub>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.</p> <p>Methods</p> <p>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 <it>HTR3A </it>c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the <it>5-HTT </it>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.</p> <p>Results</p> <p><it>HTR3A </it>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).</p> <p>Conclusions</p> <p>The <it>HTR3A </it>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-HT<sub>3 </sub>mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the <it>HTR3A </it>c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.</p>http://www.biomedcentral.com/1471-2350/12/140 |
| spellingShingle | Grobbee Diederick E Muris Jean WM Laheij Robert JF Onland-Moret N Charlotte Fransen Gerdine AJ van Marrewijk Corine J de Wit Niek J ter Linde José JM Mujakovic Suhreta Samsom Melvin Jansen Jan BMJ Knottnerus André Numans Mattijs E Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia BMC Medical Genetics |
| title | Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia |
| title_full | Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia |
| title_fullStr | Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia |
| title_full_unstemmed | Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia |
| title_short | Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia |
| title_sort | serotonin receptor 3a polymorphism c 42c t is associated with severe dyspepsia |
| url | http://www.biomedcentral.com/1471-2350/12/140 |
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