Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease.
Gastroenterology
; 133(3): 808-17, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17854592
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Predisposição Genética para Doença
/
Polimorfismo de Nucleotídeo Único
/
Receptores Acoplados a Proteínas G
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article