Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation
Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation
复制标题
DOI：
10.1152/ajpgi.00371.2007
复制
发表时间：
2008-01-01
影响因子：
4.5
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
--
作者：
Camilleri, Michael;Carlson, Paula;Zinsmeister, Alan R.
大麻素激动剂抑制胃肠蠕动。内源性大麻素anandamide被脂肪酸酰胺水解酶（FAAH）灭活。人类FAAH基因（C385 A）的单核苷酸多态性降低FAAH表达。我们的目的是评估FAAH基因型变异与功能性胃肠疾病（FGID）患者的症状表型、胃排空和胃容量、结肠传输和直肠感觉之间的关系。从2000年到2007年，482名FGID患者[罗马II阳性，159名便秘疾病，184名腹泻疾病（D-IBS），86名混合性肠功能（M-IBS），20名慢性腹痛（CAP），33名功能性消化不良]和252名健康志愿者（HV）接受了问卷调查和表型和基因型研究：250例胃排空，210例空腹和餐后胃容量，152例结肠传输，123例直肠感觉。通过TaqMan测定，所有人都具有FAAH基因型[CC与多态性（CA/AA）]。FGID和HV的FAAH基因型分布均未偏离Hardy-Weinberg平衡。FAAH基因型与FGID表型（总体卡方（2），P = 0.011）和特定个体表型（P = 0.048）显著相关。因此，FAAH CA/AA增加了D-IBS（P = 0.008）、M-IBS（P = 0.012）和可能的CAP（P = 0.055）的几率（相对于HV）。FAAH CA/AA基因型与D-IBS患者的结肠传输速度显著相关（P = 0.037）。FAAH基因型与直肠感觉阈值或等级无关。内源性大麻素代谢的遗传变异与D-IBS和M-IBS中的症状表型以及D-IBS中更快的结肠运输的相关性支持大麻素机制可能在人类结肠运动的控制中发挥作用的假设，值得进一步研究。
Cannabinoid agonist inhibits gastrointestinal motility. The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase (FAAH). A single nucleotide polymorphism in the human FAAH gene (C385A) reduces FAAH expression. Our aim was to evaluate associations between FAAH genotype variation and symptom phenotype, gastric emptying and volume, colonic transit, and rectal sensation in patients with functional gastrointestinal disorders (FGID). 482 FGID patients [Rome II positive, 159 constipation disorders, 184 diarrhea disorders (D-IBS), 86 mixed bowel function (M-IBS), 20 chronic abdominal pain (CAP), 33 functional dyspepsia], and 252 healthy volunteers (HV) underwent questionnaires and studies of phenotype and genotype from 2000 to 2007: 250 gastric emptying, 210 fasting and postprandial gastric volume, 152 colonic transit, and 123 rectal sensation. All had FAAH genotype [CC vs. polymorphic (CA/AA)] determined by TaqMan. FAAH genotype distribution of FGID patients and HV did not deviate from Hardy-Weinberg equilibrium. There was a significant association of FAAH genotype with FGID phenotype (overall chi(2), P = 0.011) and with specific individual phenotypes (P = 0.048). Thus FAAH CA/AA increases the odds (relative to HV) for D-IBS (P = 0.008), M-IBS (P = 0.012), and, possibly, CAP (P = 0.055). There was a significant association of FAAH CA/AA genotype with accelerated colonic transit in D-IBS (P = 0.037). There was no association of FAAH genotype with rectal sensation thresholds or ratings. The association of genetic variation in metabolism of endo-cannabinoids with symptom phenotype in D-IBS and M-IBS and with faster colonic transit in D-IBS supports the hypothesis that cannabinoid mechanisms may play a role in the control of colonic motility in humans and deserve further study.