Irritable bowel syndrome (IBS) is a symptomatic motility and sensory disorder of the lower gastrointestinal (GI) tract and is characterized by abdominal pain/ discomfort, bloating and altered bowel activity. It is usually classified according to the predominant bowel habit -IBS with constipation (C-IBS), IBS with diarrhoea (D-IBS) or IBS with alternating symptoms of both constipation and diarrhoea.1 Despite intensive research, the complicated and multifactorial pathophysiology underlying IBS is not completely understood. Recently, there is growing emphasis on identifying specific biological pathways that contribute to the complex pathophysiology of this disease.
SERT AND SERT POLYMORPHISMSSerotonin [5-hydroxytryptamine (5-HT)], which is released from enterochromaffin cells and enteric neurons, is a key neurotransmitter modulating various GI functions, including secretion, motility and visceral perception (reviewed by Gershon, 2 ). To prevent excessive 5-HT signalling and 5-HT receptor desensitization, the actions of enteric 5-HT are terminated by reuptake through the serotonin transporter protein (SERT).
3The relevance of serotonin reuptake for the control of GI functions was confirmed by reports of disturbed GI motility in SERT knockout mice 4 (SERT-P, originally known as 5-HTTLPR). The latter consists of a 44 base pair deletion or insertion in the 5¢ flanking promoter region, resulting in a short (s) and a long (l) allele respectively. The functional impact of VNTR is not well known, but the SERT-P polymorphism seems to be functionally relevant as it modulates SERT gene transcription and, consequently, 5-HT reuptake and availability. One study showed that compared with the homozygous long (l/l) genotype, polymorphic heterozygous (l/ s) and homozygous short (s/s) SERT-P were associated with reduced function of the transporter protein in a lymphoblastoid cell line.8 Consistent with the effects of serotonin in the gut, SERT-P polymorphisms could potentially be involved in the development of IBS. This has mainly lead to the hypothesis that the s/s and l/s SERT-P genotypes are associated with prolonged serotonergic activity, which may lead to diarrhoea.
SERT POLYMORPHISMS IN IBSTo investigate this hypothesis, several studies have tried to assess a relationship between IBS and SERT polymorphisms. A Turkish study by Pata et al. 9 reported an association of D-IBS with the l/s SERT-P genotype. In addition, the authors also described an