Barrett's esophagus associates with a variant of IL23R gene.
Gastroesophageal reflux disease is regarded as a spectrum of diseases: non-erosive reflux disease (NERD), erosive reflux disease (ERD), and the far end of the spectrum represented by patients with Barrett's esophagus. Among predisposing factors, both risk and protective polymorphic variants of several genes may influence the clinical outcomes of reflux disease. Consequently, different molecular mechanisms are likely to underlie the development of clinical variants of reflux disease. Ninety six patients with reflux disease were screened for polymorphisms of CARD15, SLC22A4 (OCTN1), SLC22A5 (OCTN2), DLG5, ATG16L1 and IL23R genes which had previously been found to associate with immune-mediated chronic inflammatory disorders. While none of the polymorphisms were associated with NERD or ERD, the 1142G/A variant of the IL23R gene was found to be a risk variant in Barrett's esophagus patients. The IL23/IL23R pathway may modulate STAT3 transcriptional activity which is an essential regulator not only of immune-mediated inflammation, but also of inflammatory-associated apoptosis resistance. Although the mechanisms of metaplastic transition of inflamed squamous epithelium are undetermined as yet, our findings suggest potential involvement of alternations in the IL23/IL23R pathway as a molecular background of Barrett's esophagus development.
Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education at the Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland.
Pawel
P
Gaj
Michal
M
Mikula
Lucjan S
LS
Wyrwicz
Jaroslaw
J
Regula
Jerzy
J
Ostrowski
D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism
C515500:IL23R protein, human; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human