[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-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.
Li
Yu-yuan
YY
Department of Gastroenterology, First People's Hospital of Guangzhou, 510180, China. liyyliyy@tom.com
Nie
Yu-qiang
YQ
Xie
Jun
J
Tan
Hui-zhen
HZ
Zhou
Yong-jian
YJ
Wang
Hong
H
D000328:Adult; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007438:Introns / Q000235:genetics; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D005765:Gastrointestinal Agents; D007211:Indoles; D050486:Serotonin Plasma Membrane Transport Proteins; C105050:tegaserod