[肠易激综合征中血清素转运体基因多态性及其对替加色罗治疗的影响]

[Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment].

作者信息

Li Yu-yuan, Nie Yu-qiang, Xie Jun, Tan Hui-zhen, Zhou Yong-jian, Wang Hong

机构信息

Department of Gastroenterology, First People's Hospital of Guangzhou, 510180, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2006 Jul;45(7):552-5.

DOI:

PMID:17074108

Abstract

OBJECTIVE

To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5-hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS); and to investigate the impact of SERT genotypes on the efficacy of 5-HT(4) receptor agonist tegaserod in constipation predominant type (C-IBS) patients.

METHODS

PCR was used to detect the genetic polymorphisms in 87 patients with IBS confirmed with Rome II criteria and 96 healthy subjects, then 41 C-IBS patients received tegaserod 6 mg twice daily for 4 weeks. Each patient recorded his or her symptoms in a diary. Efficacy was assessed by patient's experience of overall symptoms and severity of constipation before and after the treatment.

RESULTS

The 5-HTTLPR genotypes frequencies were: S/S 52.9%, S/L 31.0%, L/L 16.1% in IBS patients; and S/S 57.3%, S/L 35.4%, L/L 7.3% in control. VNTRs genotypes were STin2.10/10: 2.3%, STin2.12/10: 17.2%, STin2.12/12: 80.5% in IBS patients; and STin2.10/10: 2.1%, STin2.12/10: 11.4%, STin2.12/12: 86.5% in control. There was no significant difference in the two genotypes frequencies between IBS and control groups (P > 0.05). However, the allele frequency of the L/L genotype was significantly higher in the C-IBS group than in control (25.0% vs 7.3%, P < 0.05). The clinical responder rates of tegaserod in S/S (85.0%) and S/L (70.0%) genotypes differed significantly from that (36.4%) in L/L genotype (P < 0.05). The scores of Subject's Global Assessment of relief after treatment were: S/S 1.35 +/- 0.81, S/L 1.70 +/- 0.95 vs L/L 2.27 +/- 0.45 (P < 0.05). All other variables for assessment of efficacy including stool frequency, stool consistency and sensation of bowel complete evacuation in L/L genotype were also significantly poorer than those in S/S and S/L (P < 0.05).

CONCLUSIONS

5-HTTLPR and VNTRs genetic polymorphisms existed in Chinese people. In general, the genotypes were not involved in the pathogenesis of IBS. However people with L/L genotype were vulnerable for development of C-IBS. The 5-HTTLPR genetic polymorphisms influenced the efficacy of tegaserod treatment in C-IBS patients with L/L being poorer than S/S and S/L genotypes.

摘要

目的

研究中国人5-羟色胺（5-HT）转运体基因连锁多态性区域（5-HTTLPR）中血清素再摄取转运体（SERT）基因多态性及内含子2中可变数目串联重复序列（VNTRs），以及它们与肠易激综合征（IBS）发病机制的关系；研究SERT基因型对5-HT(4)受体激动剂替加色罗治疗便秘型（C-IBS）患者疗效的影响。

方法

采用聚合酶链反应（PCR）检测87例符合罗马II标准的IBS患者和96例健康对照者的基因多态性，然后41例C-IBS患者接受替加色罗6mg每日2次，共4周治疗。每位患者在日记中记录其症状。通过患者治疗前后总体症状体验和便秘严重程度评估疗效。

结果

IBS患者中5-HTTLPR基因型频率为：S/S 52.9%，S/L 31.0%，L/L 16.1%；对照组中S/S 57.3%，S/L 35.4%，L/L 7.3%。IBS患者中VNTRs基因型为STin2.10/10：2.3%，STin2.12/10：17.2%，STin2.12/12：80.5%；对照组中STin2.10/10：2.1%，STin2.12/10：11.4%，STin2.12/12：86.5%。IBS组和对照组两组基因型频率无显著差异（P>0.05）。然而，C-IBS组中L/L基因型的等位基因频率显著高于对照组（25.0%对7.3%，P<0.05）。替加色罗在S/S（85.0%）和S/L（70.0%）基因型中的临床有效率与L/L基因型（36.4%）有显著差异（P<0.05）。治疗后受试者总体缓解评估得分：S/S 1.35±0.81，S/L 1.70±0.95，L/L 2.27±0.45（P<0.05）。L/L基因型中所有其他疗效评估变量包括排便频率、大便性状和肠道完全排空感觉也显著低于S/S和S/L基因型（P<0.05）。