title: Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.
abstract: L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53); p = 8.48E-04 and OR = 3.02 (1.36-6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Kutszegi
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Ágnes F
authors.initials: ÁF
authors.lastname: Semsei
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Gézsi
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Judit C
authors.initials: JC
authors.lastname: Sági
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Nagy
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Csordás
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Jakab
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Lautner-Csorba
authors.affiliation: Department of Pediatrics and Pediatric Health Care Center, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Krisztina Míta
authors.initials: KM
authors.lastname: Gábor
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor T
authors.initials: GT
authors.lastname: Kovács
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Dániel J
authors.initials: DJ
authors.lastname: Erdélyi
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary; Central Laboratory, Heim Pal Children Hospital, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
mesh_terms: D000293:Adolescent; D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase