title: Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease.
abstract: OBJECTIVE
  The neuropeptide S receptor (NPSR1) gene has been associated recently with asthma and maps in a region of chromosome 7 previously linked also to inflammatory bowel disease (IBD). NPSR1 is expressed on the epithelia of several organs including the intestine, and appears to be up-regulated in inflammation. We tested NPSR1 gene polymorphism for association with IBD and verified whether the expression of its 2 major isoforms (NPSR1-A and NPSR1-B) is altered in the intestine of IBD patients.
  
  
  METHODS
  Eight NPSR1 polymorphisms were genotyped in 2490 subjects from 3 cohorts of IBD patients and controls from Italy, Sweden, and Finland. Real-time polymerase chain reaction and immunohistochemistry were used to quantify NPSR1 messenger RNA (mRNA) and protein expression in intestinal biopsy specimens from IBD patients and controls.
  
  
  RESULTS
  Global analysis of the whole dataset identified strong association of a NPSR1 haplotype block with IBD (P = .0018) and its 2 major forms: Crohn's disease (CD) (P = .026) and ulcerative colitis (UC) (P = .003). Genetic effects caused by individual haplotypes were identified mainly for the predisposing haplotype H2 in CD (P = .0005) and the protective haplotype H8 in UC (P = .003). NPSR1 mRNA and protein levels were increased in IBD patients compared with controls, and the risk haplotype H2 correlated with higher expression of both NPSR1-A (P = .024) and NPSR1-B (P = .047) mRNAs.
  
  
  CONCLUSIONS
  NPSR1 polymorphism is associated with IBD susceptibility. Specific NPSR1 alleles might act as genetic risk factors for chronic inflammatory diseases of the epithelial barrier organs.
authors.affiliation: Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden. mauro.damato@ki.se
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Sara
authors.initials: S
authors.lastname: Bruce
authors.forename: Francesca
authors.initials: F
authors.lastname: Bresso
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Sini
authors.initials: S
authors.lastname: Ezer
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindgren
authors.forename: Marco
authors.initials: M
authors.lastname: Astegiano
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Gionchetti
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riegler
authors.forename: Raffaello
authors.initials: R
authors.lastname: Sostegni
authors.forename: Marco
authors.initials: M
authors.lastname: Daperno
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Patricia
authors.initials: P
authors.lastname: Momigliano-Richiardi
authors.forename: Leif
authors.initials: L
authors.lastname: Torkvist
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: Maarit
authors.initials: M
authors.lastname: Lappalainen
authors.forename: Paulina
authors.initials: P
authors.lastname: Paavola-Sakki
authors.forename: Leena
authors.initials: L
authors.lastname: Halme
authors.forename: Martti
authors.initials: M
authors.lastname: Farkkila
authors.forename: Ulla
authors.initials: U
authors.lastname: Turunen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Robert
authors.initials: R
authors.lastname: Lofberg
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: C484532:NPSR1 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled