Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Neurogastroenterol Motil. 2011 Nov;23(11):995-9, e458. doi: 10.1111/j.1365-2982.2011.01772.x. Epub 2011 Aug 24.
The membrane bound bile acid (BA) receptor, TGR5, is located on myenteric, cholinergic and nitrergic neurons in colon and proximal small intestine. Our aim was to assess the association of genetic variation in TGR5 and small bowel transit (SBT) and colonic transit.
In 230 healthy controls and 414 patients with lower functional GI disorders [FGID: irritable bowel syndrome (IBS)-alternators (Alt) 84, IBS-constipation (IBS-C) 157, IBS-diarrhea (IBS-D) 173], we tested the association between TGR5 SNP rs11554825 (minor allele frequency 41%) with symptom phenotype (total cohort) and intermediate phenotype (SBT or colonic transit by radioscintigraphy) which was available in 213 people in this cohort. The association with symptom phenotype was assessed using logistic regression, while the association with colonic filling at 6 h (CF6), and colonic transit [geometric center (GC) at 24 h] was assessed using ancova, in each instance assuming a dominant genetic model.
There was no significant association with symptom phenotype. We observed a potential association of SNP rs11554825 with overall transit: CF6 (P = 0.061) and GC24 (P = 0.083). The association of the SNP with CF6 in the IBS-D subgroup (P = 0.017) indicated the TC/CC subgroup had an average 50% faster SBT compared with the TT subgroup. In IBS-D patients, GC24 was not significantly associated with rs11554825 (TC/CC vs TT).
CONCLUSIONS & INFERENCES: Variation in TGR5 may contribute to altered SBT and colonic transit in lower FGID. Further studies are required to characterize the potential role of BA receptor, TGR5, in the mechanism and treatment of bowel dysfunction in lower FGID.
膜结合胆汁酸（BA）受体 TGR5 位于结肠和近端小肠的肌间、胆碱能和氮能神经元上。我们的目的是评估 TGR5 基因变异与小肠转运（SBT）和结肠转运的相关性。
在 230 名健康对照者和 414 名下胃肠道功能障碍患者[FGID：交替型肠易激综合征（IBS）-交替者（Alt）84 例、IBS-便秘型（IBS-C）157 例、IBS-腹泻型（IBS-D）173 例]中，我们检测了 TGR5 SNP rs11554825（次要等位基因频率为 41%）与症状表型（总队列）和中间表型（SBT 或放射性闪烁照相法测量的结肠转运）之间的相关性，该队列中 213 人具有该中间表型数据。使用逻辑回归评估与症状表型的相关性，使用协方差分析（ancova）评估与 6 小时结肠充盈（CF6）和结肠转运[24 小时几何中心（GC）]的相关性，在每种情况下均假设显性遗传模型。
与症状表型无显著相关性。我们观察到 SNP rs11554825 与整体转运之间存在潜在相关性：CF6（P=0.061）和 GC24（P=0.083）。SNP 与 IBS-D 亚组 CF6 的相关性（P=0.017）表明，TC/CC 亚组的 SBT 比 TT 亚组快 50%。在 IBS-D 患者中，GC24 与 rs11554825 无显著相关性（TC/CC 与 TT）。
TGR5 的变异可能导致下胃肠道功能障碍中 SBT 和结肠转运的改变。需要进一步研究以阐明 BA 受体 TGR5 在治疗下胃肠道功能障碍中的作用机制。
