The relationship between the val158met catechol-O-methyltransferase (COMT) polymorphism and irritable bowel syndrome.
The relationship between the val158met catechol-O-methyltransferase (COMT) polymorphism and irritable bowel syndrome.
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DOI：
10.1371/journal.pone.0018035
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Norrback KF
中科院分区：
文献类型：
--
作者：
Karling P;Danielsson Å;Wikgren M;Söderström I;Del-Favero J;Adolfsson R;Norrback KF
儿茶酚-O-甲基转移酶(COMT)在儿茶酚胺的降解过程中起着关键作用，其功能多态性为val158met。与MET/MET基因相比，Val/Val基因的酶活性高出三到四倍，而Val/MET基因的酶活性居中。由于疼痛症状以及焦虑和抑郁分别与COMT活性低和高相关，而这些情况都与肠易激综合征(IBS)相关，因此我们首次试图探讨COMT基因多态性与IBS的关系。对867名具有代表性的人群(445名女性)和70名IBS患者(61名女性)进行val158met基因分型，并填写医院焦虑抑郁量表(HADS)和IBS症状日记。Val/Val基因型在肠易激综合征患者中的发生率显著高于对照组(30%vs20%；CHI2(1)3.98；p = 0.046)，而Val/Met基因型在肠易激综合征患者中的发生率有降低趋势(39%vs49%；CHI2(1)2.89；p = 0.089)。在肠易激综合征患者中，VAL/VAL携带者与其他携带者(VAL/MET+MET/MET携带者)相比，排便不全的比例较低(41%比68%；CHI2(1)4.3；p = 0.04)，且排便频率显著增加(2.6vs1.8；CHI2(1)5.3；p = 0.03)。Val/Val携带者出现硬便比例较低(0%比15%；CHI2(1)3.2；p = 为0.08)，餐后排便频率较高(26%比21%；CHI2(1)3.0；p = 0.08)。在这项研究中，我们发现val158met COMT基因的Val/Val基因型与IBS以及IBS患者特定的IBS相关肠型之间存在关联。
The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS. 867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary. There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08). In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.
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