Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits
Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits
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DOI：
10.1152/ajpgi.00376.2012
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发表时间：
2013-03-01
影响因子：
4.5
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
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作者：
Camilleri, Michael;Kolar, Gururaj J.;Zinsmeister, Alan R.
[10]李文，李文.大麻素受体1基因与肠易激综合征：表型和数量性状。美国生理学杂志胃肠和肝脏生理学304：G553-G560，2013年。首次发表于2013年1月10日; doi：10.1152/ajpgi.00376.2012.-内源性大麻素代谢和CNR 1（大麻素1受体基因）的遗传变异与肠易激综合征（IBS）的症状表型、结肠传输和左结肠动力相关。我们的目的是评估CNR 1基因型（rs 806378和[AAT]n三联体）的两种变异与455例IBS患者和228例健康对照者的症状表型、小肠和结肠传输以及直肠感觉之间的关联。小肠和结肠传输通过直肠造影测量，直肠感觉通过等压扩张测量。基于显性遗传模型，通过卡方检验（症状表型）和ANCOVA（数量性状）评估与基因型的关联。CNR 1 rs 806378（而非CNR 1 [AAT]n）基因型与症状表型显著相关（χ 2 = 0.028）。在IBS-腹泻（IBS-D）组中，CNR 1 rs 806378（P = 0.014; CC vs. CT/TT）与结肠转运显著相关; TT组在24和48 h具有最快的结肠转运。CNR 1 rs 806378与气体感觉等级（P = 0.025）而非疼痛存在显著的总体关联;气体等级的最强关联在IBS-D（P = 0.002）和IBS交替（P = 0.025）亚组中。对于CNR 1（AAT）n，在24（P = 0.06）和48 h（P = 0.002）和气体（P = 0.046，IBS-D最高，P = 0.034）时观察到结肠运输的基因-表型相互作用，但没有疼痛感;与运输的最强关联是在对照组中，而不是在IBS中。这些数据支持大麻素受体可能在人类结肠运输和感觉控制中发挥作用的假设，并值得进一步研究作为低功能胃肠道疾病的潜在介质或治疗靶点。
Camilleri M, Kolar GJ, Vazquez-Roque MI, Carlson P, Burton DD, Zinsmeister AR. Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits. Am J Physiol Gastrointest Liver Physiol 304: G553-G560, 2013. First published January 10, 2013; doi:10.1152/ajpgi.00376.2012.-Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by chi(2) test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model. Significant association of CNR1 rs806378 (but not CNR1 [AAT]n) genotype and symptom phenotype was observed (chi(2) P = 0.028). There was significant association of CNR1 rs806378 (P = 0.014; CC vs. CT/TT) with colonic transit in IBS-diarrhea (IBS-D) group; the TT group had the fastest colonic transit at 24 and 48 h. There was significant overall association of CNR1 rs806378 with sensation rating of gas (P = 0.025), but not pain; the strongest associations for gas ratings were in IBS-D (P = 0.002) and IBS-alternating (P = 0.025) subgroups. For CNR1 (AAT)n, gene-by-phenotype interactions were observed for colonic transit at 24 (P = 0.06) and 48 h (P = 0.002) and gas (P = 0.046, highest for IBS-D, P = 0.034), but not pain sensation; the strongest association with transit was in controls, not in IBS. These data support the hypothesis that cannabinoid receptors may play a role in control of colonic transit and sensation in humans and deserve further study as potential mediators or therapeutic targets in lower functional gastrointestinal disorders.