title: Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases.
abstract: BACKGROUND
  The substance P pathway modulates neuroimmune interactions during intestinal inflammation.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Surgery, IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tavano
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Fabio Francesco
authors.initials: FF
authors.lastname: di Mola
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
authors.forename: Francesca Paola
authors.initials: FP
authors.lastname: Burbaci
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corritore
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Augello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Merla
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.forename: Pierluigi
authors.initials: P
authors.lastname: di Sebastiano
mesh_terms: D000328:Adult; D001004:Anus Diseases / Q000150:complications / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015260:Neprilysin / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D012907:Smoking / Q000378:metabolism; D013373:Substance P / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D013373:Substance P; D015260:Neprilysin
keywords: Inflammatory bowel disease; Neurokinin-1 receptor; Neutral endopeptidase; Substance P