Serotonin re-uptake transporter gene polymorphisms are associated with imatinib-induced diarrhoea in chronic myeloid leukaemia patients.
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ adverse effects
Dasatinib
/ adverse effects
Diarrhea
/ chemically induced
Female
Gene Frequency
Humans
Imatinib Mesylate
/ adverse effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Male
Middle Aged
Minisatellite Repeats
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Serotonin Plasma Membrane Transport Proteins
/ genetics
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
15
09
2019
accepted:
24
04
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
15
1
2021
Statut:
epublish
Résumé
Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukaemia (CML), can cause lower gastrointestinal (GI) toxicity which is manifested as diarrhoea. The mechanisms are not fully understood. The enteroendocrine signalling compound, serotonin (5-HT), is important for regulating peristaltic motion, fluid secretion and visceral hypersensitivity in the GI tract, and has been implicated in diseases such as irritable bowel syndrome. In this study, we have evaluated whether TKI-induced diarrhoea may be related to variation in the serotonin re-uptake transporter (SERT) gene. CML patients with and without diarrhoea on the SPIRIT2 trial (imatinib, n = 319; and dasatinib, n = 297) were genotyped for the promoter 5-HTTLPR, intron 2 VNTR and rs25531 polymorphisms by PCR-based methods. Diarrhoea was more prevalent in imatinib, than in dasatinib treated patients (P = 0.015), which when stratified by gender was seen to be driven by female patients (P = 0.036). Logistic regression analysis revealed that age, and the dominant HTTLPR with the rs25531 single nucleotide polymorphism (SNP) model, explained the occurrence of diarrhoea in ~10% of imatinib-treated female CML patients. These data suggest SERT polymorphisms influence imatinib-induced diarrhoea but not that of dasatinib.
Identifiants
pubmed: 32439979
doi: 10.1038/s41598-020-65350-0
pii: 10.1038/s41598-020-65350-0
pmc: PMC7242433
doi:
Substances chimiques
Antineoplastic Agents
0
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
Imatinib Mesylate
8A1O1M485B
Dasatinib
RBZ1571X5H
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8394Subventions
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
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