A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia
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Future Medicine Ltd.
Abstract
Aim: To evaluate the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia. Methods: A total of 189 children treated for acute lymphoblastic leukemia were genotyped for four SNPs with allele discrimination assays. The incidence and timing of radiologically confirmed symptomatic grade 4 osteonecrosis were classified based on the Ponte di Legno toxicity working group consensus definition. Results: Thirteen children developed grade 4 osteonecrosis (6.8%), of whom 12 received the intermediate/high-risk treatment protocol. GRIN3A variant allele carriers had to stop dexamethasone therapy earlier resulting in significantly shorter duration of dexamethasone treatment (mean [95% CI]: 75.17 [64.28-86.06] vs 85.90 [81.22-90.58] weeks; p = 0.054) and lower cumulative dose (mean [95% CI]: 1118.11 [954.94-1281.29] vs 1341.14 [1264.17-1418.11] mg/m2; p = 0.011). Conclusion: This is the first pharmacogenomics evaluation of the association between GRIN3A variants and glucocorticoid-induced osteonecrosis in Arab children. © 2021
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Acute lymphoblastic leukemia, Arab, Children, Dexamethasone, Genetic polymorphisms, Glucocorticoids, Grin3a, Osteonecrosis, Pharmacogenetics, Child, Genotype, Humans, Polymorphism, single nucleotide, Precursor cell lymphoblastic leukemia-lymphoma, Receptors, n-methyl-d-aspartate, Anthracycline, Asparaginase, Cyclophosphamide, Cytarabine, Mercaptopurine, Methotrexate, Vincristine, Glucocorticoid, Grin3a protein, human, N methyl dextro aspartic acid receptor, Acp1 gene, Allele, Article, Blood flow, Bone necrosis, Bone tissue, Cohort analysis, Controlled study, Disease classification, Drug megadose, Drug substitution, Drug withdrawal, Female, Gene location, Genetic association, Genetic predisposition, Genetic variability, Grik1 gene, Grin3a gene, Heterozygote, High risk patient, Human, Human tissue, Incidence, Long term exposure, Major clinical study, Male, Oncogene, Patient participation, Pharmacogenomics, Phase 1 clinical trial, Phase 2 clinical trial, Practice guideline, Retrospective study, School child, Sh3yl1 gene, Single nucleotide polymorphism, Treatment duration, Genetics