Abstract
5HTTLPR polymorphism of serotonin transporter yields short (S) and long (L) alleles. SS and LS genotypes are associated with reduced expression of serotonin transporter. This cross-sectional study investigated the association of 5HTTLPR with symptom severity of irritable bowel syndrome (IBS). Patients with IBS (Rome III) and healthy controls were included. Genomic DNA was extracted from saliva, and 5HTTLPR alleles were assessed by polymerase chain reaction. IBS symptom severity was evaluated by means of IBS-SSS questionnaire. Two hundreds and four IBS patients (159 females; mean age: 39.6±12.3 years; 106 with constipation: C-IBS; 98 with diarrhea: D-IBS) and 200 healthy controls (154 females; mean age: 40.4±15.8 years) were enrolled. The overall IBS-SSS value was higher in LS/SS than LL patients (319.0±71.5 versus 283.8±62.3; P = 0.0006). LS/SS patients had also higher values of abdominal pain (59.7±21.0 versus 51.0±18.8; P = 0.020) and bowel dissatisfaction (80.1±23.9 versus 70.5±22.8; P = 0.035). The overall IBS-SSS values in C-IBS and D-IBS patients were 317.2±68.3 and 296.1±71.4, respectively (P = 0.192), with significantly higher values for abdominal distension (65.0±24.4 versus 51.4±24.8; P = 0.0006), but not for bowel dissatisfaction (80.5±21.7 versus 72.9±25.7; P = 0.138). Frequencies of 5HTTLPR genotypes did not differ significantly when comparing IBS patients (overall or upon stratification in C-IBS and D-IBS) with healthy controls. In conclusion, the LS and SS genotypes are significantly correlated with IBS symptom severity, although their possible direct causal role remains to be proven. In addition, the present findings do not support an association of 5HTTLPR with IBS or its clinical presentation in terms of bowel habit predominance.
Highlights
The promoter region of human SERT gene contains a polymorphism, designated as ‘5-HT transporter length polymorphic region’ (5HTTLPR), which consists of a 44-base pair deletion/insertion, resulting in a short (S) and long (L) allele. [17,18] The implications of this polymorphism in Irritable bowel syndrome (IBS) are currently under evaluation since, as compared with LL genotype, SS or SL genotypes are associated with lower levels of SERT mRNA transcripts, and thereby lower levels of SERT expression and lower efficiency of 5-HT reuptake. [19,20,21] A meta-analysis of association studies has not supported a pathogenic link of 5HTTLPR with IBS
[22] By contrast, some studies have found a significant association when IBS patients were stratified by their predominant bowel habit, [23] or were investigated for pain sensation at rectal distension or somatic symptom scores. [10,24] whether 5HTTLPR exerts any influence on symptom severity in IBS remains undetermined
When comparing the mean values obtained for each IBS-SSS item, ‘abdominal pain severity’ and ‘bowel dissatisfaction’ were significantly higher in patients with LS/SS than LL genotype, while no significant differences were found with regard for the ‘occurrence of pain over the preceding 10 days’, ‘abdominal distension severity’, and ‘interference with quality of life’ (Table 1)
Summary
Irritable bowel syndrome (IBS) is a functional digestive disorder characterized by abdominal pain/discomfort and changes in bowel habit (constipation and/or diarrhoea), which can be associated with alterations of gastrointestinal (GI) transit, visceral hypersensitivity and psychopathological comorbidities. [1,2] Owing to its chronicity and substantial lack of effective cures, IBS results in a significant social burden, with a loss of work productivity, impaired quality of life, and a remarkable use of health care resources. [3]. [4,5] Based on current evidence, a gene-environment paradigm has been proposed for IBS, whereby a combination of genetic determinants and environmental factors gives rise to alterations in GI sensation and motor functions, that account for the occurrence of symptoms. [19,20,21] A meta-analysis of association studies has not supported a pathogenic link of 5HTTLPR with IBS. [22] By contrast, some studies have found a significant association when IBS patients were stratified by their predominant bowel habit, [23] or were investigated for pain sensation at rectal distension or somatic symptom scores. The present study was carried out with the primary purpose of investigating a possible association of 5HTTLPR polymorphism with overall symptom severity in IBS patients
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