Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases

Francesca Tavano, Orazio Palmieri, Fabio Francesco di Mola, Anna Latiano, Francesca Paola Burbaci, Maria Rosa Valvano, Giuseppe Corritore, Bartolomeo Augello, Giuseppe Merla, Vito Annese, Angelo Andriulli, Pierluigi di Sebastiano

Research output: Contribution to journalArticle

Abstract

Background: The substance P pathway modulates neuroimmune interactions during intestinal inflammation. Aims: To analyse mucosal expression and genetic variants of the genes coding for substance P, neurokinin-1 receptor and neutral endopeptidase in patients with inflammatory bowel disease. Methods: qRT-PCR was used to analyse mRNA levels in matched, paired samples of inflamed colonic mucosa and adjacent non-inflamed endoscopic tissue from 26 Crohn's disease and 25 ulcerative colitis patients. Allele and genotype frequencies of tag-SNPs were determined in 908 Crohn's disease, 929 ulcerative colitis, and 853 controls. Expression levels and genotype distributions were examined within patients' clinical sub-phenotypes. Results: All 3 evaluated genes were overexpressed in inflamed tissues from Crohn's disease (P=0.033, P=4×10-5, P=0.001), while in ulcerative colitis only higher levels of the gene coding for neutral endopeptidase were statistically significant (P=2.5×10-5). Smoking habit and perianal disease were significantly associated with substance P (P=0.002) and neurokinin-1 receptor levels (P=0.02) in Crohn's disease. Neutral endopeptidase rs701109 variant was associated with inflammatory bowel disease (Crohn's disease: P=0.022; ulcerative colitis: P=0.045), and with the need for colectomy in ulcerative colitis (P=0.008, OR=2.46, 95% CI=1.27-4.76). Conclusions: Genetic variants of the gene coding for neutral endopeptidase might affect the neuroimmune interaction during intestinal inflammation and influence clinical sub-phenotypes in patients with inflammatory bowel disease.

Original languageEnglish
Pages (from-to)1003-1010
Number of pages8
JournalDigestive and Liver Disease
Volume45
Issue number12
DOIs
Publication statusPublished - Dec 2013

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Keywords

  • Inflammatory bowel disease
  • Neurokinin-1 receptor
  • Neutral endopeptidase
  • Substance P

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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