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

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-HT4 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 RomeⅡcriteria 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% , STinZ 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.