Genetic variation in thelymphotoxin-α(LTA)/tumour necrosis factor-α(TNFα) locus as a risk factor for idiopathic achalasia
| Autor: | Severine Vermeire, Ana G. Vigo, Johannes Schumacher, Markus M. Nöthen, Mira M. Wouters, Elena Urcelay, Giovanni Zaninotto, Anna Latiano, Julio Perez de la Serna, Guy E. Boeckxstaens, Jessica Becker, Manuel Mattheisen, Luigi Laghi, Diether Lambrechts, Vito Annese, Michael Knapp, Rosario Cuomo, Hauke Lang, Wout O. Rohof, Uberto Fumagalli, Antonio Ruiz de León, Isabelle Cleynen, Giovanni Sarnelli, Michaela Mueller, Jan Tack, Ines Gockel, Orazio Palmieri |
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| Přispěvatelé: | Wouters, Mm, Lambrechts, D, Becker, J, Cleynen, I, Tack, J, Vigo, Ag, Ruiz de Leon, A, Urcelay, E, Perez de la Serna, J, Rohof, W, Annese, V, Latiano, A, Palmieri, O, Mattheisen, M, Mueller, M, Lang, H, Fumagalli, U, Laghi, L, Zaninotto, G, Cuomo, Rosario, Sarnelli, Giovanni, Nothen, Mm, Vermeire, S, Knapp, M, Gockel, I, Schumacher, J, Boeckxstaens, Ge, Gastroenterology and Hepatology |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Genetic Markers Pathology medicine.medical_specialty Genotyping Techniques Achalasia Single-nucleotide polymorphism Locus (genetics) Genetic polymorphisms Polymorphism Single Nucleotide digestive system Cohort Studies Pathogenesis Risk Factors Genetic variation Genotype otorhinolaryngologic diseases Humans Medicine SNP Genetic Predisposition to Disease Allele Lymphotoxin-alpha Tumor Necrosis Factor-alpha business.industry Gastroenterology Middle Aged medicine.disease digestive system diseases Esophageal Achalasia Logistic Models Case-Control Studies Immunology Female business |
| Zdroj: | Wouters, M M, Lambrechts, D, Becker, J, Cleynen, I, Tack, J, Vigo, A G, Ruiz de León, A, Urcelay, E, Pérez de la Serna, J, Rohof, W, Annese, V, Latiano, A, Palmieri, O, Mattheisen, M, Mueller, M, Lang, H, Fumagalli, U, Laghi, L, Zaninotto, G, Cuomo, R, Sarnelli, G, Nöthen, M M, Vermeire, S, Knapp, K M, Gockel, I, Schumacher, J & Boeckxstaens, G E 2013, ' Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia ', Gut . https://doi.org/10.1136/gutjnl-2013-304848 Gut, 63(9), 1401-1409. BMJ Publishing Group |
| ISSN: | 1468-3288 0017-5749 1401-1409 |
| DOI: | 10.1136/gutjnl-2013-304848 |
| Popis: | BACKGROUND: Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors predisposing to achalasia have been poorly documented, we assessed whether single nucleotide polymorphisms (SNPs) in genes mediating immune response and neuronal function contribute to achalasia susceptibility. METHODS: 391 SNPs covering 190 immune and 67 neuronal genes were genotyped in an exploratory cohort from Central Europe (589 achalasia patients, 794 healthy volunteers (HVs)). 24 SNPs (p0.2) were genotyped in the exploratory cohort. Genotype distributions of patients (1030) and HVs (1368) were compared using Cochran-Armitage trend test. RESULTS: The rs1799724 SNP located between the lymphotoxin-α (LTA) and tumour necrosis factor-α (TNFα) genes was significantly associated with achalasia and withstood correction for testing multiple SNPs (p=1.17E-4, OR=1.41 (1.18 to 1.67)). SNPs in high LD with rs1799724 were associated with achalasia. Three SNPs located in myosin-5B, adrenergic receptor-β-2 and interleukin-13 (IL13) showed nominally significant association to achalasia that was strengthened by replication. CONCLUSIONS: Our study provides evidence for rs1799724 at the LTA/TNFα locus as a susceptibility factor for idiopathic achalasia. Additional studies are needed to dissect which genetic variants in the LTA/TNFα locus are disease-causing and confirm other variants as potential susceptibility factors for achalasia. ispartof: Gut vol:63 issue:9 pages:1401-1409 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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