A Study of Candidate Genotypes Associated with Dyspepsia in a U.S. Community

Camilleri, Christopher E; Carlson, Paula; Camilleri, Michael; Castillo, E. J.; Locke, G. Richard; Geno, Debra M.; Stephens, Debra; Zinsmeister, Alan R.; Urrutia, Raúl

doi:10.1111/j.1572-0241.2006.00481.x

Cited by 95 publications

(136 citation statements)

References 58 publications

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“…In one study 118 of polymorphisms in candidate genes for different 5-HT receptors, cholecystokinin receptors and GNB3 as well as in the promoters of the genes encoding cholecystokinin and the sodium-dependent serotonin transporter, only the role of GNB3 in functional dyspepsia was confirmed.…”

Section: Genetic Contributionsmentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

253

247

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| Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation. NATURE REVIEWS | DISEASE PRIMERS VOLUME 3 | ARTICLE NUMBER 17081 | 1 PRIMER © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .standard therapy for gastro -oesophageal reflux disease. Paediatric dyspeptic symptoms are being addressed in a separate classification effort 10 . This Primer covers functional dyspepsia in adults only, although we sporadically refer to paediatric functional dyspepsia when similarities exist. EpidemiologyThe population prevalence of functional dyspepsia is quite variable across the globe, with overall high numbers (10-40%) in Western countries and low numbers (5-30%) in Asia, independent of the respective functional dyspepsia definitions 11 . A large-scale health and nutrition survey from France 12 (which involved >35,000 people) identified that 15% of individuals had suspected functional dyspepsia, 28% had irritable bowel syndrome (IBS) and 6% had both. The population of patients who are affected by both IBS and functional dyspepsia has been reported to range between 10% and 27% in previous studies 13 and to approach 30% in popu lation samples; it could be even higher in specific populations 14,15 . This observation has given rise to the term 'overlap syndrome' (REF. 13), which calls into question the sensitivity and specificity of the Rome criteria, at least for IBS and functional dyspepsia. This argument is also supported by the observation that patients with functional dyspepsia m...

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Section: Genetic Contributionsmentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

253

247

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“…There are also several studies that have pointed out significant associations between SERT polymorphism and IBS [29][30][31][32][33] . To our knowledge, the only result that confirms the relevance of SERT polymorphisms in relation to dyspeptic symptoms comes from studies of postprandial distress syndrome [8] , while at least two other investigations failed to detect significant associations [34][35][36][37] . Gene expression levels have previously been described in dyspeptic female patients [7] , where decreased SERT expression was found in the patient group.…”

Section: Discussionmentioning

confidence: 95%

Duodenal epithelial transport in functional dyspepsia: Role of serotonin

Witte

D’Amato

Poulsen

et al. 2013

WJGP

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AB performed the research with the exception of PCR experiments and the histological staining process and analysed as well as summarized the data; Knuhtsen S performed the endoscopic examinations and assisted in characterizing patients and controls; Bindslev N and Hansen MB provided technical guidance and facilities for biopsy sampling and Ussing experiments; D'Amato M and Laurent A performed the expression studies; Poulsen SS contributed with histological evaluation and guidance in the field; Schmidt PT participated in the data analysis and held overall responsibility for ethical and economic aspects; all authors participated in the revision of the manuscript and approved the final version. The following genes were highly expressed: 5-HT receptor HTR 3E, HTR4 , HTR7 , SERT gene (SLC6A4 ) and TPH1 . Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031). CONCLUSION:Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.© 2013 Baishideng. All rights reserved.

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“…It was observed that IL-17 and migratory inhibitory factor (MIF) have an important role in the inflammatory response to H. pylori and may affect the development of functional dyspepsia in H. pylori infected subjects but there was no association of 779TC of CCK-1 intron 1 polymorphism with functional dyspepsia in US community [25]. Similarly 1676T allele carriers of cyclooxygenase-1 (cox-1) was associated with developing gastric ulcer but not associated with functional dyspepsis [27].…”

Section: Genetics Aspect Of Functional Dyspepsiamentioning

confidence: 92%

“…The association between SERT polymorphism and functional dyspepsia was explored in two studies; however they showed no significant association between them [25,26]. It was observed that IL-17 and migratory inhibitory factor (MIF) have an important role in the inflammatory response to H. pylori and may affect the development of functional dyspepsia in H. pylori infected subjects but there was no association of 779TC of CCK-1 intron 1 polymorphism with functional dyspepsia in US community [25].…”

Section: Genetics Aspect Of Functional Dyspepsiamentioning

confidence: 99%

Functional Dyspepsia: An Unresolved Issue

Mehboob¹

2015

Intern Med

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Functional dyspepsia (FD) is one of the commonest medical problems which affect the quality of life. Due to its global presentation variety of symptoms recorded, therefore no global consensus developed. The recorded symptoms of functional dyspepsia are nonspecific and the pathophysiology is diverse. The role of genetics in the susceptibility of FD is still not well established. The last Rome III criteria defined the FD as symptoms of epigastric pain or discomfort, early satiety and postprandial fullness with in the last three months with symptoms not less than six months. Patient cannot have any evidence of structural disease and predominant Gastro esophageal reflux symptoms. Failure to respond to 'test and treat approach' is also categorize as FD. A universally effective treatment for functional dyspepsia remains elusive. The purpose of this paper is to highlight the details in perspective of functional dyspepsia.

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A Study of Candidate Genotypes Associated with Dyspepsia in a U.S. Community

Abstract: Meal-unrelated dyspepsia in a U.S. community study is associated with the homozygous 825T or C alleles of GNbeta3 protein. Candidate genes controlling adrenergic, serotonergic, and CCKergic functions do not appear to be associated with dyspepsia.

Cited by 95 publications

References 58 publications

Functional dyspepsia

Functional dyspepsia

Duodenal epithelial transport in functional dyspepsia: Role of serotonin

Functional Dyspepsia: An Unresolved Issue

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