Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease

Mauro D'Amato; Sara Bruce; Francesca Bresso; Marco Zucchelli; Sini Ezer; Ville Pulkkinen; Cecilia Lindgren; Marco Astegiano; Mario Rizzetto; Paolo Gionchetti; Gabriele Riegler; Raffaello Sostegni; Marco Daperno; Sandra D'Alfonso; Patricia Momigliano-Richiardi; Leif Torkvist; Pauli Puolakkainen; Maarit Lappalainen; Paulina Paavola-Sakki; Leena Halme; Martti Farkkila; Ulla Turunen; Kimmo Kontula; Robert Lofberg; Sven Pettersson; Juha Kere

doi:10.1053/j.gastro.2007.06.012

Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease

Mauro D'Amato, Sara Bruce, Francesca Bresso, Marco Zucchelli, Sini Ezer, Ville Pulkkinen, Cecilia Lindgren, Marco Astegiano, Mario Rizzetto, Paolo Gionchetti, Gabriele Riegler, Raffaello Sostegni, Marco Daperno, Sandra D'Alfonso, Patricia Momigliano-Richiardi, Leif Torkvist, Pauli Puolakkainen, Maarit Lappalainen, Paulina Paavola-Sakki, Leena HalmeMartti Farkkila, Ulla Turunen, Kimmo Kontula, Robert Lofberg, Sven Pettersson, Juha Kere

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	808-817
Number of pages	10
Journal	Gastroenterology
Volume	133
Issue number	3
DOIs	https://doi.org/10.1053/j.gastro.2007.06.012
Publication status	Published - 1 Jan 2007
Externally published	Yes

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10.1053/j.gastro.2007.06.012

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D'Amato, M., Bruce, S., Bresso, F., Zucchelli, M., Ezer, S., Pulkkinen, V., Lindgren, C., Astegiano, M., Rizzetto, M., Gionchetti, P., Riegler, G., Sostegni, R., Daperno, M., D'Alfonso, S., Momigliano-Richiardi, P., Torkvist, L., Puolakkainen, P., Lappalainen, M., Paavola-Sakki, P., ... Kere, J. (2007). Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease. Gastroenterology, 133(3), 808-817. https://doi.org/10.1053/j.gastro.2007.06.012

D'Amato, Mauro ; Bruce, Sara ; Bresso, Francesca ; Zucchelli, Marco ; Ezer, Sini ; Pulkkinen, Ville ; Lindgren, Cecilia ; Astegiano, Marco ; Rizzetto, Mario ; Gionchetti, Paolo ; Riegler, Gabriele ; Sostegni, Raffaello ; Daperno, Marco ; D'Alfonso, Sandra ; Momigliano-Richiardi, Patricia ; Torkvist, Leif ; Puolakkainen, Pauli ; Lappalainen, Maarit ; Paavola-Sakki, Paulina ; Halme, Leena ; Farkkila, Martti ; Turunen, Ulla ; Kontula, Kimmo ; Lofberg, Robert ; Pettersson, Sven ; Kere, Juha. / Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease. In: Gastroenterology. 2007 ; Vol. 133, No. 3. pp. 808-817.

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title = "Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease",

abstract = "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.",

author = "Mauro D'Amato and Sara Bruce and Francesca Bresso and Marco Zucchelli and Sini Ezer and Ville Pulkkinen and Cecilia Lindgren and Marco Astegiano and Mario Rizzetto and Paolo Gionchetti and Gabriele Riegler and Raffaello Sostegni and Marco Daperno and Sandra D'Alfonso and Patricia Momigliano-Richiardi and Leif Torkvist and Pauli Puolakkainen and Maarit Lappalainen and Paulina Paavola-Sakki and Leena Halme and Martti Farkkila and Ulla Turunen and Kimmo Kontula and Robert Lofberg and Sven Pettersson and Juha Kere",

year = "2007",

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doi = "10.1053/j.gastro.2007.06.012",

language = "English",

volume = "133",

pages = "808--817",

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D'Amato, M, Bruce, S, Bresso, F, Zucchelli, M, Ezer, S, Pulkkinen, V, Lindgren, C, Astegiano, M, Rizzetto, M, Gionchetti, P, Riegler, G, Sostegni, R, Daperno, M, D'Alfonso, S, Momigliano-Richiardi, P, Torkvist, L, Puolakkainen, P, Lappalainen, M, Paavola-Sakki, P, Halme, L, Farkkila, M, Turunen, U, Kontula, K, Lofberg, R, Pettersson, S & Kere, J 2007, 'Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease', Gastroenterology, vol. 133, no. 3, pp. 808-817. https://doi.org/10.1053/j.gastro.2007.06.012

Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease. / D'Amato, Mauro; Bruce, Sara; Bresso, Francesca; Zucchelli, Marco; Ezer, Sini; Pulkkinen, Ville; Lindgren, Cecilia; Astegiano, Marco; Rizzetto, Mario; Gionchetti, Paolo; Riegler, Gabriele; Sostegni, Raffaello; Daperno, Marco; D'Alfonso, Sandra; Momigliano-Richiardi, Patricia; Torkvist, Leif; Puolakkainen, Pauli; Lappalainen, Maarit; Paavola-Sakki, Paulina; Halme, Leena; Farkkila, Martti; Turunen, Ulla; Kontula, Kimmo; Lofberg, Robert; Pettersson, Sven; Kere, Juha.

In: Gastroenterology, Vol. 133, No. 3, 01.01.2007, p. 808-817.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease

AU - D'Amato, Mauro

AU - Bruce, Sara

AU - Bresso, Francesca

AU - Zucchelli, Marco

AU - Ezer, Sini

AU - Pulkkinen, Ville

AU - Lindgren, Cecilia

AU - Astegiano, Marco

AU - Rizzetto, Mario

AU - Gionchetti, Paolo

AU - Riegler, Gabriele

AU - Sostegni, Raffaello

AU - Daperno, Marco

AU - D'Alfonso, Sandra

AU - Momigliano-Richiardi, Patricia

AU - Torkvist, Leif

AU - Puolakkainen, Pauli

AU - Lappalainen, Maarit

AU - Paavola-Sakki, Paulina

AU - Halme, Leena

AU - Farkkila, Martti

AU - Turunen, Ulla

AU - Kontula, Kimmo

AU - Lofberg, Robert

AU - Pettersson, Sven

AU - Kere, Juha

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

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U2 - 10.1053/j.gastro.2007.06.012

DO - 10.1053/j.gastro.2007.06.012

M3 - Article

C2 - 17854592

AN - SCOPUS:34548535911

VL - 133

SP - 808

EP - 817

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -

Neuropeptide S Receptor 1 Gene Polymorphism Is Associated With Susceptibility to Inflammatory Bowel Disease

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