Document Detail


Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3).
MedLine Citation:
PMID:  19174793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Visceral hypersensitivity is involved in the etiology of reflux symptoms. Familial clustering and twin studies demonstrated a genetic predisposition to gastroesophageal reflux disease (GERD). G-protein-coupled receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral factors modulating esophageal sensory function. Thus, polymorphisms in G-proteins are putative genetic factors contributing to GERD manifestation. A functional polymorphism in the G-protein beta3 subunit gene (GNB3) is associated with functional dyspepsia (FD), in which visceral hypersensitivity is implicated in symptom generation. We evaluated the association of the GNB3 C825T polymorphism with GERD and GERD subgroups classified according to esophageal acid exposure time, symptom-reflux correlation, or coexistence of FD and/or irritable bowel syndrome (IBS) symptoms. METHODS: In total, 363 GERD patients, defined as having esophageal pH < 4 > or = 6% of time and/or symptom index (SI) > or = 50% or symptom association probability (SAP) > or = 95%, participated. In addition, 373 healthy controls free of gastrointestinal symptoms were studied. Genotyping was performed by molecular beacon assay. RESULTS: The CT genotype was more prevalent in GERD patients relative to healthy controls (adjusted odds ratio (OR)=1.43, 95% CI 1.04-1.98). GERD patients sensitive to physiological amounts of reflux displayed a higher OR (1.59), as did GERD patients with a positive symptom association score (1.50). The strongest association was detected in patients without concomitant FD and/or IBS symptoms (OR=1.66). CONCLUSIONS: GERD is associated with GNB3 C825T. The results for GERD subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele, underlies this association.
Authors:
D R de Vries; J J M ter Linde; M A van Herwaarden; A J P M Smout; M Samsom
Related Documents :
18264013 - Prognostic modelling in ischaemic stroke study, additional value of genetic characteris...
19458483 - Ercc5 promoter polymorphisms at -763 and +25 predict the response to oxaliplatin-based ...
7814013 - Pku in slovakia: mutation screening and haplotype analysis.
Publication Detail:
Type:  Journal Article     Date:  2009-01-20
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  104     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-04     Completed Date:  2009-03-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  281-5     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. d.r.devries@umcutrecht.nl
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Body Mass Index
Case-Control Studies
Dyspepsia / complications
Esophageal pH Monitoring
Female
Gastroesophageal Reflux / complications,  genetics*
Genetic Predisposition to Disease
Heterotrimeric GTP-Binding Proteins / genetics*
Humans
Irritable Bowel Syndrome / complications
Male
Middle Aged
Polymorphism, Genetic / genetics*
Chemical
Reg. No./Substance:
0/G-protein beta3 subunit; EC 3.6.5.1/Heterotrimeric GTP-Binding Proteins
Comments/Corrections
Comment In:
Am J Gastroenterol. 2009 Feb;104(2):286-8   [PMID:  19174788 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with...
Next Document:  Importance of gender, socioeconomic status, and history of abuse on patient preference for endoscopi...