神经肽S受体1基因多态性与炎症性肠病易感性相关。

Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease.

作者信息

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

机构信息

Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden.

出版信息

Gastroenterology. 2007 Sep;133(3):808-17. doi: 10.1053/j.gastro.2007.06.012. Epub 2007 Jun 20.

DOI:10.1053/j.gastro.2007.06.012

PMID: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.

摘要

背景与目的

神经肽S受体（NPSR1）基因最近被发现与哮喘有关，并且定位于7号染色体上的一个区域，该区域先前也与炎症性肠病（IBD）相关。NPSR1在包括肠道在内的多个器官的上皮细胞中表达，并且在炎症中似乎上调。我们测试了NPSR1基因多态性与IBD的相关性，并验证了其两种主要异构体（NPSR1-A和NPSR1-B）在IBD患者肠道中的表达是否改变。

方法

对来自意大利、瑞典和芬兰的3个IBD患者队列和对照的2490名受试者进行了8种NPSR1多态性的基因分型。使用实时聚合酶链反应和免疫组织化学来定量IBD患者和对照的肠道活检标本中NPSR1信使核糖核酸（mRNA）和蛋白质的表达。

结果

对整个数据集的综合分析确定了一个NPSR1单倍型模块与IBD有强相关性（P = 0.0018）及其两种主要形式：克罗恩病（CD）（P = 0.026）和溃疡性结肠炎（UC）（P = 0.003）。个体单倍型引起的遗传效应主要在CD中的易感单倍型H2（P = 0.0005）和UC中的保护性单倍型H8（P = 0.003）中被发现。与对照相比，IBD患者中NPSR1 mRNA和蛋白质水平升高，风险单倍型H2与NPSR1-A（P = 0.024）和NPSR1-B（P = 0.047）mRNA的更高表达相关。