便秘型肠易激综合征的SERT基因多态性及其与患者临床疗效的关系

目的探讨便秘型肠易激综合征(C-IBS)5-羟色胺转运蛋白(SERT)基因多态性及其与替加色罗临床疗效的关系。方法利用PCR检测84例符合罗马Ⅲ诊断标准的C-IBS患者和103例健康对照者外周血的SERT启动子区域(5-HTTLPR)与第2内含子可变数目串联重复序列(VNTRs)两个基因多态性,对其中入选65例的C-IBS患者给予4周替加色罗6 mg、2次/d,评估治疗前后患者临床症状及便秘程度。结果 C-IBS患者L/L基因型频率比对照组明显升高(25.0%vs 7.8%,P<0.05)。治疗后C-IBS患者各基因型组替加色罗治疗的有效率有统计学差异差异,表现为总体疗效和单个症状改善S/S基因型和S/L基因型均优于L/L基因型(S/S 93.1%、S/L 70.6%、L/L 33.3%,P<0.01)。结论 SERT基因多态性可能与C-IBS相关;SERT基因多态性影响替加色罗对C-IBS患者的疗效。

Sertotonin-transporter polymorphism in constipation-predominanti irritable bowel syndrome and its influence on clinical effect of tegaserod

Objective To investigate the potential association between the serotonin reuptake transporter(SERT) polymorphisms and the constipation predominant irritable bowel syndrome(C-IBS) phenotype,also to investigate the impact of SERT genotypes on the efficacy of 5-HT4 receptor agonist tegaserod in constipation predominant type patients.Methods PCR was used to detect the 5-HTTLPR and VNTRs polymorphisms of SERT gene in 84 patients with C-IBS confirmed with Rome Ⅲ criteria and 103 healthy subjects,then 61 C-IBS patients received tegaserod 6 mg twice daily for 4 weeks.Patients recorded their symptoms in a diary.Efficacy was assessed by patient’s overall symptoms of IBS and severity of constipation before and after tegaserod treatment.Results There was significant difference between patients and controls on genotypes of the 5-HTTLPR gene(P<0.01),and the allele frequencies of the 5-HTTLPR allele L/L genotype was significantly higher in the constipation predominant IBS(C-IBS) group than in the controls(25% vs 7.8%,P<0.05).The clinical responder rates of tegaserod in S/S and S/L genotypes significantly differed from those in L/L genotype(S/S 93.1%,S/L 70.6%,L/L 33.3%,P<0.01).Conclusions The 5-HTTLPR polymorphisms of SERT gene were probably associated with C-IBS.SERT gene polymorphisms influenced the efficacy of tegaserod in C-IBS patients.