5-HTTLPR and STin2 polymorphisms in the serotonin transporter gene and irritable bowel syndrome: effect of bowel habit and sex

Niesler, Beate; Kapeller, Johannes; Fell, Catherine; Atkinson, Wendy; Möller, Dorothée; Fischer, Christine; Whorwell, Peter J.; Houghton, Lesley A.

doi:10.1097/meg.0b013e32832e9d6b

Cited by 41 publications

(31 citation statements)

References 31 publications

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“…The 10/12 genotype has been associated with IBS in one study (114). However, at least five other studies found no association between STin2 VNTR and IBS (65,73,88,90,121).…”

Section: Neurotransmitter Mechanismsmentioning

confidence: 95%

“…While the prevalence of IBS in India appears to be higher in men than in women (43), it is unclear why sex would explain the association of the SS genotype (for a gene located on chromosome 17, rather than an X or a Y chromosome) with C-IBS. A study that included patients with IBS from Germany and the United Kingdom [where prevalence is ϳ1.3-1.5:1 in women compared with men (38,47)] showed a lower prevalence of the SS genotype in IBS and, particularly, in diarrhea-predominant IBS (D-IBS), but this was only observed in male patients (34 male IBS patients and 30 male controls) (88).…”

Section: Neurotransmitter Mechanismsmentioning

confidence: 99%

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Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

Camilleri

Katzka

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

102

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The objectives of this review are twofold. Our first objective is to evaluate the evidence supporting a role for genetics in irritable bowel syndrome (IBS). Specific examples of the associations of genetic variation and symptoms, syndromes, and intermediate phenotypes, including neurotransmitter (serotonergic, ␣ 2-adrenergic, and cannabinoid) mechanisms, inflammatory pathways (IL-10, TNF␣, GN␤3, and susceptibility loci involved in Crohn's disease), and bile acid metabolism, are explored. The second objective is to review pharmacogenetics in IBS, with the focus on cytochrome P-450 metabolism of drugs used in IBS, modulation of motor and sensory responses to serotonergic agents based on the 5-hydroxytryptamine (5-HT) transporter-linked polymorphic region (5-HTTLPR) and 5-HT3 genetic variants, responses to a nonselective cannabinoid agonist (dronabinol) based on cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) variation, and responses to a bile acid (sodium chenodeoxycholate) and bile acid binding (colesevelam) based on klotho␤ (KLB) and fibroblast growth factor receptor 4 (FGFR4) variation. Overall, there is limited evidence of a genetic association with IBS; the most frequently studied association is with 5-HTTLPR, and the most replicated association is with TNF superfamily member 15. Most of the pharmacogenetic associations are reported with intermediate phenotypes in relatively small trials, and confirmation in large clinical trials using validated clinical end points is still required. No published genome-wide association studies in functional gastrointestinal or motility disorders have been published. adrenergic; serotonergic; solute carrier 6A4; 5-hydroxytryptamine transporter-linked polymorphic region; inflammation; susceptibility; klotho␤; bile acid malabsorption EPIDEMIOLOGICAL STUDIES of familial aggregation (57, 99) and twins (7,70,72,82,83) suggest a genetic contribution to irritable bowel syndrome (IBS). While the data are conflicting, they are generally consistent with the hypothesis that IBS may be a complex genetic disorder. Understanding of genetic variation and its influence on gut motility, secretion, sensation, and inflammation, as it is applied to IBS, has the potential to help elucidate mechanisms of control of a poorly understood syndrome. Similarly, the impact of genetic variation on the targets of therapy in IBS may enhance the efficacy of pharmacological therapies. These targets include receptors and regulators of gut function and variations in drug metabolism.This review addresses the available literature on the role of genetics in IBS. There are no published genome-wide association studies in functional gastrointestinal (GI) or motility disorders specifically focusing on genetic epidemiology and pharmacogenetics. Genetic Epidemiology of IBS: Candidate Gene ApproachAs the general approach followed in genotype association studies (Fig. 1), investigators have sought the relationship between genotype and clinical phenotype, while appreciating that intermediaries, such as th...

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“…The 10/12 genotype has been associated with IBS in one study (114). However, at least five other studies found no association between STin2 VNTR and IBS (65,73,88,90,121).…”

Section: Neurotransmitter Mechanismsmentioning

confidence: 95%

Section: Neurotransmitter Mechanismsmentioning

confidence: 99%

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

Camilleri

Katzka

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

102

View full text Add to dashboard Cite

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“…The LL genotype has also been associated with constipationpredominant IBS (C-IBS) [11], whereas the ss genotype has been associated with increased IBS incidence in women [12] and with C-IBS [5]. Interestingly, many studies do not associate SERT polymorphism with IBS [9,13,14], whereas a recent study suggests that male D-IBS patients have a reduced frequency of the 5-HTTLPR ss genotype [15].…”

Section: Introductionmentioning

confidence: 99%

Serotonin Transporter and G Protein Beta 3 Subunit Gene Polymorphisms in Greeks with Irritable Bowel Syndrome

et al. 2011

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“…Three studies have examined another SERT gene polymorphism, designated as STin2 (located in intron 2 and consisting of a variable number -usually 9, 10 or 12 -of nearly identical 17bp repeats), for which any association with IBS or its clinical variants was not found (undetermined ethnicity, 26 [61][62][63]. In addition, Kohen et al [62] extended their search to 179A>G (currently 1936A>G), a SNP located immediately upstream of 5HTTLPR with opposite effects on SERT expression, showing a positive association of the G allele with IBS.…”

Section: Serotoninmentioning

confidence: 99%

Genetics and Pharmacogenetics of Aminergic Transmitter Pathways in Functional Gastrointestinal Disorders

et al. 2015

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Functional gastrointestinal disorders (FGIDs) are highly prevalent syndromes, without evident underlying organic causes. Their pathogenesis is multifactorial in nature, with a combination of environmental and genetic factors contributing to their clinical manifestations, for which most of current treatments are not satisfactory. It is acknowledged that amine mediators (noradrenaline, dopamine and serotonin) play pivotal regulatory actions on gut functions and visceral sensation. In addition, drugs of therapeutic interest for FGIDs act on these transmitter pathways. The present article reviews current knowledge on the impact of genetics and pharmacogenetics of aminergic pathways on FGID pathophysiology, clinical presentations, symptom severity and medical management, in an attempt of highlighting the most relevant evidence and point out issues that should be addressed in future investigations.

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5-HTTLPR and STin2 polymorphisms in the serotonin transporter gene and irritable bowel syndrome: effect of bowel habit and sex

Cited by 41 publications

References 31 publications

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

Serotonin Transporter and G Protein Beta 3 Subunit Gene Polymorphisms in Greeks with Irritable Bowel Syndrome

Genetics and Pharmacogenetics of Aminergic Transmitter Pathways in Functional Gastrointestinal Disorders

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