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Published in: Digestive Diseases and Sciences 8/2014

01-08-2014 | Original Article

Association of Genetic Variants in GNβ3 with Functional Dyspepsia: A Meta-Analysis

Authors: Fei Dai, Yaping Liu, Haitao Shi, Shuqiong Ge, Jun Song, Lei Dong, Jingyun Yang

Published in: Digestive Diseases and Sciences | Issue 8/2014

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Abstract

Background

Functional dyspepsia (FD) is a functional upper gastrointestinal disorder. The etiology and pathogenesis of FD remain unclear, with genetic factors playing an important role. Previous studies investigated the association of C825T in GNβ3 with FD, with conflicting results reported.

Aims

The aim of this meta-analysis is to assess the association of genetic variants in GNβ3 with FD.

Methods

We performed a systematic literature search in PubMed, Cochrane Library, Google Scholar, and Web of Knowledge, and conducted a meta-analysis to assess the association of C825T in GNβ3 with FD. For sensitivity analysis, we analyzed the association between C825T and subtypes of FD. We also performed meta-analyses separately for individual ethnic groups/countries of origin.

Results

A total of eight studies met the eligibility criteria and were included in our analyses. Our meta-analysis finds no association between 825CC and FD (OR 1.19, 95 % CI 0.84–1.67, p = 0.328). However, the association is significant under an additive model (OR 0.59, 95 % CI 0.38–0.92, p = 0.018). Sensitivity analysis indicated a significant association of C825T with FD in participants from Korea but not in those from Japan, Europe, or the United States. We also detected a significant association of this SNP with dysmotility.

Conclusions

The genetic variant C825T in GNβ3 is significantly associated with FD under an additive model and the association is race-specific. Further studies with larger samples sizes are needed to validate our findings and to explore the potential mechanism underlying the association.
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Literature
1.
go back to reference Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ III. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology. 1992;102:1259–1268.PubMed Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ III. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology. 1992;102:1259–1268.PubMed
2.
go back to reference Heikkinen M, Farkkila M. What is the long-term outcome of the different subgroups of functional dyspepsia? Aliment Pharmacol Ther. 2003;18:223–229.PubMedCrossRef Heikkinen M, Farkkila M. What is the long-term outcome of the different subgroups of functional dyspepsia? Aliment Pharmacol Ther. 2003;18:223–229.PubMedCrossRef
3.
go back to reference Agreus L, Svardsudd K, Talley NJ, Jones MP, Tibblin G. Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study. Am J Gastroenterol. 2001;96:2905–2914.PubMedCrossRef Agreus L, Svardsudd K, Talley NJ, Jones MP, Tibblin G. Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study. Am J Gastroenterol. 2001;96:2905–2914.PubMedCrossRef
4.
go back to reference Geeraerts B, Tack J. Functional dyspepsia: past, present, and future. J Gastroenterol. 2008;43:251–255.PubMedCrossRef Geeraerts B, Tack J. Functional dyspepsia: past, present, and future. J Gastroenterol. 2008;43:251–255.PubMedCrossRef
5.
go back to reference Tack J, Masclee A, Heading R, et al. A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia. Neurogastroenterol Motil. 2009;21:272–280.PubMedCrossRef Tack J, Masclee A, Heading R, et al. A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia. Neurogastroenterol Motil. 2009;21:272–280.PubMedCrossRef
6.
go back to reference Miwa H. Why dyspepsia can occur without organic disease: pathogenesis and management of functional dyspepsia. J Gastroenterol. 2012;47:862–871.PubMedCrossRef Miwa H. Why dyspepsia can occur without organic disease: pathogenesis and management of functional dyspepsia. J Gastroenterol. 2012;47:862–871.PubMedCrossRef
7.
go back to reference Greydanus MP, Vassallo M, Camilleri M, Nelson DK, Hanson RB, Thomforde GM. Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Gastroenterology. 1991;100:1311–1318.PubMed Greydanus MP, Vassallo M, Camilleri M, Nelson DK, Hanson RB, Thomforde GM. Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Gastroenterology. 1991;100:1311–1318.PubMed
8.
go back to reference Ford AC. Eradicating Helicobacter pylori in functional dyspepsia. Gastroenterology. 2012;142:1613–1614.PubMedCrossRef Ford AC. Eradicating Helicobacter pylori in functional dyspepsia. Gastroenterology. 2012;142:1613–1614.PubMedCrossRef
9.
go back to reference Shaib Y, El-Serag HB. The prevalence and risk factors of functional dyspepsia in a multiethnic population in the United States. Am J Gastroenterol. 2004;99:2210–2216.PubMedCrossRef Shaib Y, El-Serag HB. The prevalence and risk factors of functional dyspepsia in a multiethnic population in the United States. Am J Gastroenterol. 2004;99:2210–2216.PubMedCrossRef
10.
go back to reference Mahadeva S, Goh KL. Anxiety, depression and quality of life differences between functional and organic dyspepsia. J Gastroenterol Hepatol. 2011;26:49–52.PubMedCrossRef Mahadeva S, Goh KL. Anxiety, depression and quality of life differences between functional and organic dyspepsia. J Gastroenterol Hepatol. 2011;26:49–52.PubMedCrossRef
11.
go back to reference Li Y, Nie Y, Sha W, Su H. The link between psychosocial factors and functional dyspepsia: an epidemiological study. Chin Med J. 2002;115:1082–1084.PubMed Li Y, Nie Y, Sha W, Su H. The link between psychosocial factors and functional dyspepsia: an epidemiological study. Chin Med J. 2002;115:1082–1084.PubMed
12.
go back to reference Locke GR III, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ III. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000;75:907–912.PubMedCrossRef Locke GR III, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ III. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000;75:907–912.PubMedCrossRef
13.
go back to reference Morris-Yates A, Talley NJ, Boyce PM, Nandurkar S, Andrews G. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol. 1998;93:1311–1317.PubMedCrossRef Morris-Yates A, Talley NJ, Boyce PM, Nandurkar S, Andrews G. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol. 1998;93:1311–1317.PubMedCrossRef
14.
go back to reference Holtmann G, Siffert W, Haag S, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971–979.PubMedCrossRef Holtmann G, Siffert W, Haag S, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971–979.PubMedCrossRef
15.
go back to reference Camilleri CE, Carlson PJ, Camilleri M, et al. A study of candidate genotypes associated with dyspepsia in a U.S. community. Am J Gastroenterol. 2006;101:581–592.PubMedCrossRef Camilleri CE, Carlson PJ, Camilleri M, et al. A study of candidate genotypes associated with dyspepsia in a U.S. community. Am J Gastroenterol. 2006;101:581–592.PubMedCrossRef
16.
go back to reference Arisawa T, Tahara T, Shibata T, et al. Genetic polymorphisms of cyclooxygenase-1 (COX-1) are associated with functional dyspepsia in Japanese women. J Women’s Health. 2008;17:1039–1043.CrossRef Arisawa T, Tahara T, Shibata T, et al. Genetic polymorphisms of cyclooxygenase-1 (COX-1) are associated with functional dyspepsia in Japanese women. J Women’s Health. 2008;17:1039–1043.CrossRef
17.
go back to reference Tahara T, Arisawa T, Shibata T, Nakamura M, Wang F, Hirata I. COMT gene val158met polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology. 2008;55:979–982.PubMed Tahara T, Arisawa T, Shibata T, Nakamura M, Wang F, Hirata I. COMT gene val158met polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology. 2008;55:979–982.PubMed
18.
go back to reference Baumgart D, Naber C, Haude M, et al. G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation. Circ Res. 1999;85:965–969.PubMedCrossRef Baumgart D, Naber C, Haude M, et al. G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation. Circ Res. 1999;85:965–969.PubMedCrossRef
19.
go back to reference Oshima T, Nakajima S, Yokoyama T, et al. The G-protein beta3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010;11:13.PubMedCentralPubMedCrossRef Oshima T, Nakajima S, Yokoyama T, et al. The G-protein beta3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010;11:13.PubMedCentralPubMedCrossRef
20.
go back to reference Kim HG, Lee KJ, Lim SG, Jung JY, Cho SW. G-protein beta3 subunit C825T polymorphism in patients with overlap syndrome of functional dyspepsia and irritable bowel syndrome. J Neurogastroenterol Motil. 2012;18:205–210.PubMedCentralPubMedCrossRef Kim HG, Lee KJ, Lim SG, Jung JY, Cho SW. G-protein beta3 subunit C825T polymorphism in patients with overlap syndrome of functional dyspepsia and irritable bowel syndrome. J Neurogastroenterol Motil. 2012;18:205–210.PubMedCentralPubMedCrossRef
22.
go back to reference Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet. 1999;354:1896–1900.PubMedCrossRef Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet. 1999;354:1896–1900.PubMedCrossRef
23.
go back to reference Shimpuku M, Futagami S, Kawagoe T, et al. G-protein beta3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese. Neurogastroenterol Motil. 2011;23:1073–1080.PubMedCrossRef Shimpuku M, Futagami S, Kawagoe T, et al. G-protein beta3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese. Neurogastroenterol Motil. 2011;23:1073–1080.PubMedCrossRef
24.
go back to reference van Lelyveld N, Linde JT, Schipper M, Samsom M. Candidate genotypes associated with functional dyspepsia. Neurogastroenterol Motil. 2008;20:767–773.PubMedCrossRef van Lelyveld N, Linde JT, Schipper M, Samsom M. Candidate genotypes associated with functional dyspepsia. Neurogastroenterol Motil. 2008;20:767–773.PubMedCrossRef
25.
go back to reference Tahara T, Arisawa T, Shibata T, et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig Dis Sci. 2008;53:642–646.PubMedCrossRef Tahara T, Arisawa T, Shibata T, et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig Dis Sci. 2008;53:642–646.PubMedCrossRef
26.
go back to reference Park CS, Uhm JH. Polymorphisms of the serotonin transporter gene and G-protein beta3 subunit gene in Korean children with irritable bowel syndrome and functional dyspepsia. Gut Liver. 2012;6:223–228.PubMedCentralPubMedCrossRef Park CS, Uhm JH. Polymorphisms of the serotonin transporter gene and G-protein beta3 subunit gene in Korean children with irritable bowel syndrome and functional dyspepsia. Gut Liver. 2012;6:223–228.PubMedCentralPubMedCrossRef
27.
go back to reference Park MI. Is there enough evidence for the association of gNbeta3 C825T polymorphism with functional dyspepsia and irritable bowel syndrome? J Neurogastroenterol Motil. 2012;18:348–349.PubMedCentralPubMedCrossRef Park MI. Is there enough evidence for the association of gNbeta3 C825T polymorphism with functional dyspepsia and irritable bowel syndrome? J Neurogastroenterol Motil. 2012;18:348–349.PubMedCentralPubMedCrossRef
28.
go back to reference Hegele RA, Harris SB, Hanley AJ, Cao H, Zinman B. G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji-Cree. Hypertension. 1998;32:688–692.PubMedCrossRef Hegele RA, Harris SB, Hanley AJ, Cao H, Zinman B. G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji-Cree. Hypertension. 1998;32:688–692.PubMedCrossRef
29.
go back to reference Siffert W, Rosskopf D, Siffert G, et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet. 1998;18:45–48.PubMedCrossRef Siffert W, Rosskopf D, Siffert G, et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet. 1998;18:45–48.PubMedCrossRef
30.
go back to reference Gollasch M, Kleuss C, Hescheler J, Wittig B, Schultz G. Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. Proc Natl Acad Sci USA. 1993;90:6265–6269.PubMedCentralPubMedCrossRef Gollasch M, Kleuss C, Hescheler J, Wittig B, Schultz G. Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. Proc Natl Acad Sci USA. 1993;90:6265–6269.PubMedCentralPubMedCrossRef
31.
go back to reference Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B. Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature. 1991;353:43–48.PubMedCrossRef Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B. Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature. 1991;353:43–48.PubMedCrossRef
32.
go back to reference Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B. Different beta-subunits determine G-protein interaction with transmembrane receptors. Nature. 1992;358:424–426.PubMedCrossRef Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B. Different beta-subunits determine G-protein interaction with transmembrane receptors. Nature. 1992;358:424–426.PubMedCrossRef
33.
go back to reference Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B. Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins. Science. 1993;259:832–834.PubMedCrossRef Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B. Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins. Science. 1993;259:832–834.PubMedCrossRef
34.
go back to reference Andresen V, Camilleri M, Kim HJ, et al. Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders? Gastroenterology. 2006;130:1985–1994.PubMedCrossRef Andresen V, Camilleri M, Kim HJ, et al. Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders? Gastroenterology. 2006;130:1985–1994.PubMedCrossRef
35.
go back to reference Siffert W, Forster P, Jockel KH, et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol. 1999;10:1921–1930.PubMed Siffert W, Forster P, Jockel KH, et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol. 1999;10:1921–1930.PubMed
36.
go back to reference Hegele RA, Anderson C, Young TK, Connelly PW. G-protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit. Genome Res. 1999;9:972–977.PubMedCentralPubMedCrossRef Hegele RA, Anderson C, Young TK, Connelly PW. G-protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit. Genome Res. 1999;9:972–977.PubMedCentralPubMedCrossRef
37.
go back to reference Dong Y, Zhu H, Sagnella GA, Carter ND, Cook DG, Cappuccio FP. Association between the C825T polymorphism of the G protein beta3-subunit gene and hypertension in blacks. Hypertension. 1999;34:1193–1196.PubMedCrossRef Dong Y, Zhu H, Sagnella GA, Carter ND, Cook DG, Cappuccio FP. Association between the C825T polymorphism of the G protein beta3-subunit gene and hypertension in blacks. Hypertension. 1999;34:1193–1196.PubMedCrossRef
38.
go back to reference Sartori M, Semplicini A, Siffert W, et al. G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives. Hypertension. 2003;42:909–914.PubMedCrossRef Sartori M, Semplicini A, Siffert W, et al. G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives. Hypertension. 2003;42:909–914.PubMedCrossRef
39.
go back to reference Klintschar M, Stiller D, Schwaiger P, Kleiber M. DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight. Forensic Sci Int. 2005;153:142–146.PubMedCrossRef Klintschar M, Stiller D, Schwaiger P, Kleiber M. DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight. Forensic Sci Int. 2005;153:142–146.PubMedCrossRef
40.
go back to reference Morrison AC, Doris PA, Folsom AR, Nieto FJ, Boerwinkle E. G-protein beta3 subunit and alpha-adducin polymorphisms and risk of subclinical and clinical stroke. Stroke. 2001;32:822–829.PubMedCrossRef Morrison AC, Doris PA, Folsom AR, Nieto FJ, Boerwinkle E. G-protein beta3 subunit and alpha-adducin polymorphisms and risk of subclinical and clinical stroke. Stroke. 2001;32:822–829.PubMedCrossRef
41.
go back to reference Wascher TC, Paulweber B, Malaimare L, et al. Associations of a human G protein beta3 subunit dimorphism with insulin resistance and carotid atherosclerosis. Stroke. 2003;34:605–609.PubMedCrossRef Wascher TC, Paulweber B, Malaimare L, et al. Associations of a human G protein beta3 subunit dimorphism with insulin resistance and carotid atherosclerosis. Stroke. 2003;34:605–609.PubMedCrossRef
42.
go back to reference Zill P, Baghai TC, Zwanzger P, et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. NeuroReport. 2000;11:1893–1897.PubMedCrossRef Zill P, Baghai TC, Zwanzger P, et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. NeuroReport. 2000;11:1893–1897.PubMedCrossRef
43.
go back to reference Holtmann G, Gschossmann J, Neufang-Huber J, Gerken G, Talley NJ. Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls. Gut. 2000;47:332–336.PubMedCentralPubMedCrossRef Holtmann G, Gschossmann J, Neufang-Huber J, Gerken G, Talley NJ. Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls. Gut. 2000;47:332–336.PubMedCentralPubMedCrossRef
44.
go back to reference Camilleri M, Busciglio I, Carlson P, et al. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol. 2008;295:G219–G225. Camilleri M, Busciglio I, Carlson P, et al. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol. 2008;295:G219–G225.
45.
go back to reference Delgado-Aros S, Camilleri M, Cremonini F, Ferber I, Stephens D, Burton DD. Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology. 2004;127:1685–1694.PubMedCrossRef Delgado-Aros S, Camilleri M, Cremonini F, Ferber I, Stephens D, Burton DD. Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology. 2004;127:1685–1694.PubMedCrossRef
Metadata
Title
Association of Genetic Variants in GNβ3 with Functional Dyspepsia: A Meta-Analysis
Authors
Fei Dai
Yaping Liu
Haitao Shi
Shuqiong Ge
Jun Song
Lei Dong
Jingyun Yang
Publication date
01-08-2014
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 8/2014
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-014-3057-y

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