The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and its influence on tegaserod treatment in Chinese patients.
The aims of this study were to investigate the relationship of genetic polymorphisms of the serotonin reuptake transporter and the clinical subtypes of irritable bowel syndrome and its influence on the efficacy of tegaserod in Chinese irritable bowel syndrome patients with constipation. Genetic polymorphisms were analyzed in 87 patients and 96 controls, then 41 irritable bowel syndrome patients with constipation received tegaserod for 4 weeks. The primary efficacy variable was the responder rate measured by Subject's Global Assessment of Relief. Secondary efficacy assessed the changes of individual symptoms weekly. There was no significant difference in genotype frequencies between the patients as a whole and the control group. The frequency of the L/L genotype in the serotonin transporter gene-linked polymorphic region was significantly higher in patients with constipation than in controls (25.0% vs. 7.3%). Responder rates to tegaserod were significantly higher in the S/S (85.0%) and L/S (70.0%) than in the L/L genotype (36.4%). All secondary variables also significantly improved in the S/S and L/S groups compared to the L/L group. This study suggests the hypothesis that individuals with the L/L genotype are vulnerable to development of irritable bowel syndrome with constipation, and patients with the L/L genotype respond poorly to treatment with a routine dose of tegaserod.
Li
Yuyuan
Y
Department of Gastroenterology and Hepatology, First Municipal People's Hospital of Guangzhou, Guangzhou Medical College, 1 Panfu Road, Guangzhou, 510180, P R China.
Nie
Yuqiang
Y
Xie
Jun
J
Tang
Weizhan
W
Liang
Peizhi
P
Sha
Weihong
W
Yang
Hui
H
Zhou
Yonyjian
Y
D000328:Adult; D000483:Alleles; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D005260:Female; D005765:Gastrointestinal Agents; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D016896:Treatment Outcome
D005765:Gastrointestinal Agents; D007211:Indoles; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C105050:tegaserod; D004247:DNA