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

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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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References

  1. Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ III. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology. 1992;102:1259–1268.

    CAS  PubMed  Google Scholar 

  2. Heikkinen M, Farkkila M. What is the long-term outcome of the different subgroups of functional dyspepsia? Aliment Pharmacol Ther. 2003;18:223–229.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. Geeraerts B, Tack J. Functional dyspepsia: past, present, and future. J Gastroenterol. 2008;43:251–255.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Miwa H. Why dyspepsia can occur without organic disease: pathogenesis and management of functional dyspepsia. J Gastroenterol. 2012;47:862–871.

    Article  PubMed  Google Scholar 

  7. 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.

    CAS  PubMed  Google Scholar 

  8. Ford AC. Eradicating Helicobacter pylori in functional dyspepsia. Gastroenterology. 2012;142:1613–1614.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  10. Mahadeva S, Goh KL. Anxiety, depression and quality of life differences between functional and organic dyspepsia. J Gastroenterol Hepatol. 2011;26:49–52.

    Article  PubMed  Google Scholar 

  11. 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  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. 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.

    CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  20. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. van Lelyveld N, Linde JT, Schipper M, Samsom M. Candidate genotypes associated with functional dyspepsia. Neurogastroenterol Motil. 2008;20:767–773.

    Article  PubMed  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. 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.

    CAS  Google Scholar 

  45. 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.

    Article  PubMed  Google Scholar 

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Acknowledgments

Dr. Yang’s research was supported by R01AG036042 and the Illinois Department of Public Health.

Conflict of interest

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Authors and Affiliations

  1. Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

    Fei Dai, Haitao Shi, Shuqiong Ge & Lei Dong

  2. Division of Gastroenterology, First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Yaping Liu

  3. Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China

    Jun Song

  4. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA

    Jingyun Yang

  5. Department of Neurological Sciences, Rush University Medical Center, 600 South Paulina, Suite 1029, Chicago, IL, 60612, USA

    Jingyun Yang

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  1. Fei Dai
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Correspondence to Jingyun Yang.

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Dai, F., Liu, Y., Shi, H. et al. Association of Genetic Variants in GNβ3 with Functional Dyspepsia: A Meta-Analysis. Dig Dis Sci 59, 1823–1830 (2014). https://doi.org/10.1007/s10620-014-3057-y

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  • DOI: https://doi.org/10.1007/s10620-014-3057-y

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