Neuropeptide S receptor induces neuropeptide expression and associates with intermediate phenotypes of functional gastrointestinal disorders.
Neuropeptide S receptor induces neuropeptide expression and associates with intermediate phenotypes of functional gastrointestinal disorders.
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DOI：
10.1053/j.gastro.2009.08.051
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发表时间：
2010-01
期刊：
影响因子：
29.4
通讯作者：
D'Amato M
中科院分区：
文献类型：
--
作者：
Camilleri M;Carlson P;Zinsmeister AR;McKinzie S;Busciglio I;Burton D;Zucchelli M;D'Amato M
NPSR1是神经肽S （NPS）的受体，由胃肠道（GI）肠内分泌（EE）细胞表达，参与炎症、焦虑和伤害感受。NPSR1多态性与哮喘和炎症性肠病有关。我们的目的是确定NPS是否诱导GI神经肽的表达；并将NPSR1单核苷酸多态性（snp）与健康和功能性GI疾病（FGID）的症状表型和GI功能联系起来。real-time PCR检测NPS对转染npsr1的HEK293细胞中神经肽mRNA表达的影响。从466名FGID患者和233名健康对照的区域队列中，699名受试者成功地对17个NPSR1 snp进行了基因分型。使用性别校正回归分析和错误发现率（FDR）校正来寻找关联。NPS-NPSR1信号通路诱导CCK、VIP、PYY和生长抑素的表达增加。与FGID症状的表型无显著关联。有几个NPSR1 snp与单个运动或感觉功能相关；snp rs2609234、rs6972158和rs1379928与结肠转运率的相关性在FDR校正后仍然显著。rs1379928多态性还与36毫米汞柱膨胀时的疼痛、胀气和急迫感评分有关，这是正式测试预先指定的水平。FDR矫正后直肠感觉评分的相关性不显著。NPS-NPSR1信号通路可诱导几种神经肽的表达；NPSR1变异与FGID的结肠转运有关。NPS系统在FGID中的作用值得进一步研究。
NPSR1, the receptor for neuropeptide S (NPS), is expressed by gastrointestinal (GI) enteroendocrine (EE) cells, and is involved in inflammation, anxiety and nociception. NPSR1 polymorphisms are associated with asthma and inflammatory bowel disease. We aimed to determine whether NPS induces expression of GI neuropeptides; and to associate NPSR1 single nucleotide polymorphisms (SNPs) with symptom phenotype and GI functions in health and functional GI disorders (FGID). The effect of NPS on mRNA expression of neuropeptides was assessed using real-time PCR in NPSR1-tranfected HEK293 cells. Seventeen NPSR1 SNPs were successfully genotyped in 699 subjects from a regional cohort of 466 FGID patients and 233 healthy controls. Associations were sought using sex-adjusted regression analysis and false discovery rate (FDR) correction. NPS-NPSR1 signaling induced increased expression of CCK, VIP, PYY, and somatostatin. There were no significant associations with phenotypes of FGID symptoms. There were several NPSR1 SNPs associated with individual motor or sensory functions; the associations of SNPs rs2609234, rs6972158 and rs1379928 with colonic transit rate remained significant after FDR correction. The rs1379928 polymorphism was also associated with pain, gas and urgency sensory ratings at 36 mm Hg distension, the level pre-specified for formal testing. Associations with rectal sensory ratings were not significant after FDR correction. Expression of several neuropeptides is induced upon NPS-NPSR1 signaling; NPSR1 variants are associated with colonic transit in FGID. The role of the NPS system in FGID deserves further study.
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影响因子：
29.4
作者：
Andresen, Viola;Camilleri, Michael;Zinsmeister, Alan R.
通讯作者：
Zinsmeister, Alan R.
影响因子：
24.5
作者：
Dorn, Spencer D.;Palsson, Olafur S.;Whitehead, William E.
通讯作者：
Whitehead, William E.
影响因子：
5.8
作者：
Gonzalez, Juan R.;Armengol, Lluis;Moreno, Victor
通讯作者：
Moreno, Victor
影响因子：
12.6
作者：
Castillo, Emma Janet;Camilleri, Michael;Zinsmeister, Alan R.
通讯作者：
Zinsmeister, Alan R.
DOI：
10.1152/ajpgi.90650.2008
发表时间：
2009-03-01
影响因子：
4.5
作者：
Camilleri, Michael;Carlson, Paula;Boles, Richard G.
通讯作者：
Boles, Richard G.