Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing.

Details

Serval ID
serval:BIB_B4E86EAA3CE6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing.
Journal
Pharmacogenomics
Author(s)
Abaji R., Ceppi F., Patel S., Gagné V., Xu C.J., Spinella J.F., Colombini A., Parasole R., Buldini B., Basso G., Conter V., Cazzaniga G., Leclerc J.M., Laverdière C., Sinnett D., Krajinovic M.
ISSN
1744-8042 (Electronic)
ISSN-L
1462-2416
Publication state
Published
Issued date
10/2018
Peer-reviewed
Oui
Volume
19
Number
15
Pages
1181-1193
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
To identify genetic markers associated with vincristine-induced peripheral neuropathy (VIPN) in childhood acute lymphoblastic leukemia.
Whole-exome sequencing data were combined with exome-wide association study to identify predicted-functional germline variants associated with high-grade VIPN. Genotyping was then performed for top-ranked signals (n = 237), followed by validation in independent replication group (n = 405).
Minor alleles of rs2781377/SYNE2 (p = 0.01) and rs10513762/MRPL47 (p = 0.01) showed increased risk, whereas that of rs3803357/BAHD1 had a protective effect (p = 0.007). Using a genetic model based on weighted genetic risk scores, an additive effect of combining these loci was observed (p = 0.003). The addition of rs1135989/ACTG1 further enhanced model performance (p = 0.0001).
Variants in SYNE2, MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute lymphoblastic leukemia.
Keywords
Alleles, Child, Exome, Female, Genetic Predisposition to Disease/genetics, Genetic Variation/genetics, Genotype, Humans, Male, Peripheral Nervous System Diseases/chemically induced, Peripheral Nervous System Diseases/genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics, Risk Factors, Vincristine/adverse effects, Whole Exome Sequencing/methods, acute lymphoblastic leukemia, adverse drug reactions, association study, cancer, genetics, pharmacogenetics, polymorphism, vincristine-induced peripheral neuropathy, whole-exome sequencing
Pubmed
Web of science
Create date
19/11/2018 18:03
Last modification date
26/02/2020 6:26
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