BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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 IBDpatients. METHODS: Eight NPSR1 polymorphisms were genotyped in 2490 subjects from 3 cohorts of IBDpatients 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 IBDpatients 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 IBDpatients 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: Marco Zucchelli; Michael Camilleri; Anna Nixon Andreasson; Francesca Bresso; Aldona Dlugosz; Jonas Halfvarson; Leif Törkvist; Peter T Schmidt; Pontus Karling; Bodil Ohlsson; Richard H Duerr; Magnus Simren; Greger Lindberg; Lars Agreus; Paula Carlson; Alan R Zinsmeister; Mauro D'Amato Journal: Gut Date: 2011-06-02 Impact factor: 23.059
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Authors: Mauro D'Amato; Marco Zucchelli; Maria Seddighzadeh; Francesca Anedda; Staffan Lindblad; Juha Kere; Lars Alfredsson; Lars Klareskog; Leonid Padyukov Journal: PLoS One Date: 2010-02-22 Impact factor: 3.240