Genetic Contribution to Motility Disorders of the Upper Gastrointestinal Tract

Overview

Journal World J Gastrointest Pathophysiol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2013 Nov 19

PMID 24244875

Citations 7

Authors

Giovanni Sarnelli

Alessandra DAlessandro

Marcella Pesce

Ilaria Palumbo

Rosario Cuomo

Affiliations

Soon will be listed here.

Abstract

Motility disorders of the upper gastrointestinal tract encompass a wide range of different diseases. Esophageal achalasia and functional dyspepsia are representative disorders of impaired motility of the esophagus and stomach, respectively. In spite of their variable prevalence, what both diseases have in common is poor knowledge of their etiology and pathophysiology. There is some evidence showing that there is a genetic predisposition towards these diseases, especially for achalasia. Many authors have investigated the possible genes involved, stressing the autoimmune or the neurological hypothesis, but there is very little data available. Similarly, studies supporting a post-infective etiology, based on an altered immune response in susceptible individuals, need to be validated. Further association studies can help to explain this complex picture and find new therapeutic targets. The aim of this review is to summarize current knowledge of genetics in motility disorders of the upper gastrointestinal tract, addressing how genetics contributes to the development of achalasia and functional dyspepsia respectively.

Citing Articles

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References

Oshima T, Nakajima S, Yokoyama T, Toyoshima F, Sakurai J, Tanaka J . The G-protein beta3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010; 11:13. PMC: 2825227. DOI: 10.1186/1471-2350-11-13. View

Camilleri C, Carlson P, Camilleri M, Castillo E, Richard Locke 3rd G, Geno D . A study of candidate genotypes associated with dyspepsia in a U.S. community. Am J Gastroenterol. 2006; 101(3):581-92. DOI: 10.1111/j.1572-0241.2006.00481.x. View

Allgrove J, Clayden G, Grant D, MACAULAY J . Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet. 1978; 1(8077):1284-6. DOI: 10.1016/s0140-6736(78)91268-0. View

Everett K, Chioza B, Georgoula C, Reece A, Gardiner R, Chung E . Infantile hypertrophic pyloric stenosis: evaluation of three positional candidate genes, TRPC1, TRPC5 and TRPC6, by association analysis and re-sequencing. Hum Genet. 2009; 126(6):819-31. DOI: 10.1007/s00439-009-0735-5. View

Robertson C, Martin B, Atkinson M . Varicella-zoster virus DNA in the oesophageal myenteric plexus in achalasia. Gut. 1993; 34(3):299-302. PMC: 1374131. DOI: 10.1136/gut.34.3.299. View

Tryhus M, Davis M, Griffith J, Ablin D, Gogel H . Familial achalasia in two siblings: significance of possible hereditary role. J Pediatr Surg. 1989; 24(3):292-5. DOI: 10.1016/s0022-3468(89)80016-8. View

Santiago J, Martinez A, Benito M, Ruiz de Leon A, Mendoza J, Fernandez-Arquero M . Gender-specific association of the PTPN22 C1858T polymorphism with achalasia. Hum Immunol. 2007; 68(10):867-70. DOI: 10.1016/j.humimm.2007.07.005. View

Holtmann G, Siffert W, Haag S, Mueller N, Langkafel M, Senf W . G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004; 126(4):971-9. DOI: 10.1053/j.gastro.2004.01.006. View

Mearin F, Mourelle M, Guarner F, Salas A, Moncada S, Malagelada J . Patients with achalasia lack nitric oxide synthase in the gastro-oesophageal junction. Eur J Clin Invest. 1993; 23(11):724-8. DOI: 10.1111/j.1365-2362.1993.tb01292.x. View

10.

Tack J, Talley N, Camilleri M, Holtmann G, Hu P, Malagelada J . Functional gastroduodenal disorders. Gastroenterology. 2006; 130(5):1466-79. DOI: 10.1053/j.gastro.2005.11.059. View

11.

Stein D, Knauer C . Achalasia in monozygotic twins. Dig Dis Sci. 1982; 27(7):636-40. DOI: 10.1007/BF01297220. View

12.

Tack J, Demedts I, Dehondt G, Caenepeel P, Fischler B, Zandecki M . Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology. 2002; 122(7):1738-47. DOI: 10.1053/gast.2002.33663. View

13.

Soderhall C, Nordenskjold A . Neuronal nitric oxide synthase, nNOS, is not linked to infantile hypertrophic pyloric stenosis in three families. Clin Genet. 1998; 53(5):421-2. DOI: 10.1111/j.1399-0004.1998.tb02758.x. View

14.

Barnett J, McDonnell W, Appelman H, Dobbins W . Familial visceral neuropathy with neuronal intranuclear inclusions: diagnosis by rectal biopsy. Gastroenterology. 1992; 102(2):684-91. DOI: 10.1016/0016-5085(92)90121-e. View

15.

Everett K, Capon F, Georgoula C, Chioza B, Reece A, Jaswon M . Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16q24. Eur J Hum Genet. 2008; 16(9):1151-4. DOI: 10.1038/ejhg.2008.86. View

16.

Gockel H, Schumacher J, Gockel I, Lang H, Haaf T, Nothen M . Achalasia: will genetic studies provide insights?. Hum Genet. 2010; 128(4):353-64. DOI: 10.1007/s00439-010-0874-8. View

17.

Delgado M, Pozo D, Ganea D . The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. 2004; 56(2):249-90. DOI: 10.1124/pr.56.2.7. View

18.

Feenstra B, Geller F, Krogh C, Hollegaard M, Gortz S, Boyd H . Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis. Nat Genet. 2012; 44(3):334-7. PMC: 3693399. DOI: 10.1038/ng.1067. View

19.

Sarnelli G . Impact of genetic polymorphisms on the pathogenesis of achalasia: an age-dependent paradigm?. Neurogastroenterol Motil. 2009; 21(6):575-8. DOI: 10.1111/j.1365-2982.2009.01319.x. View

20.

Paladini F, Cocco E, Cascino I, Belfiore F, Badiali D, Piretta L . Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene. Neurogastroenterol Motil. 2009; 21(6):597-602. DOI: 10.1111/j.1365-2982.2009.01284.x. View