The Association of Serotonin Transporter Genetic Polymorphisms and Irritable Bowel Syndrome and Its Influence on Tegaserod Treatment in Chinese Patients

Abstract

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.

Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region and ADRA2A −1291C>G and Irritable Bowel Syndrome in Korea

“…28 Regarding the association with IBS subtypes, the significant association between L/L genotype and IBS-C was shown in Chinese study. 29 Similarly to our result, in another recent meta-analysis with 3,443 IBS cases and 3,359 controls of 25 studies, the L homozygote was demonstrated to be a risk factor for IBS-C development. Moreover, L allele and L/L genotype were significantly associated with increased IBS-C risk in the East Asian population.…”

“…Therefore, the possibility of type II error cannot be excluded in each polymorphism analysis, although there were some studies which demonstrated the genetic association with modest sample size. 12,13,29 Larger studies such as multi-center studies are needed for the accurate estimation of the genotypic risk. We did not perform the correction for multiple testing in order to reduce the likelihood that real effects would be missed.…”

Pharmacogenetics in irritable bowel syndrome

“…Thus, in individuals carrying 5-HTTLPR LL polymorphism in the SLC6A4 gene, alosetron is more effective in slowing colonic transit in patients with IBS-D [15]. Among patients with IBS-C, carriers of 5-HTTLPR LL are also less responsive to the 5-HT 4 agonist, tegaserod [16]. This example supports the benefit of applying a pharmacogenetics approach in a complex disease such as IBS.…”

Genetic determination of irritable bowel syndrome

“…This study suggests that individuals with the long allele genotype are vulnerable to develop IBS with constipation and respond poorly to tegaserod treatment [22] . Another study has shown that alosetron, a 5-HT type 3 receptor antagonist, relieves IBS-related pain and normalizes bowel function in women with diarrhea-predominant IBS.…”