Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases

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, neurokinin1 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 x 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 x 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. (C) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.