title: Polymorphisms in GRIA1 gene are a risk factor for asparaginase hypersensitivity during the treatment of childhood acute lymphoblastic leukemia.
abstract: l-asparaginase is an effective antineoplastic agent used in chemotherapy of acute lymphoblastic leukemia. The drug effect may be compromised by an elicited immune response, resulting in the production of anti-asparaginase antibodies causing an anaphylactic reaction or silent inactivation of the enzyme. To elucidate possible genetic predisposition for inter-individual differences in asparaginase hypersensitivity, we studied single nucleotide polymorphisms (SNPs) in the GRIA1 gene in 146 pediatric patients treated with l-asparaginase. Allergic reaction to l-asparaginase occurred in 49.3% of patients. We observed a statistically significant association between SNPs in the GRIA1 gene and the occurrence of asparaginase allergy: rs4958351 with p = 0.003, rs4958676 with p = 0.005, rs6889909 with p = 0.005, rs6890057 with p = 0.005 and rs10070447 with p = 0.006. We found a statistically significant correlation between asparaginase allergy and event-free survival (p-value 0.005).
authors.affiliation: a Department of Hematology and Oncology , University Children's Hospital , Ljubljana , Slovenia.
authors.forename: Vladan
authors.initials: V
authors.lastname: Rajić
authors.affiliation: b Unit of Special Laboratory Diagnostics, Centre for Medical Genetics, University Medical Centre Ljubljana , Ljubljana , Slovenia.
authors.forename: Maruša
authors.initials: M
authors.lastname: Debeljak
authors.affiliation: c Institute of Biochemistry, Medical Faculty, University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Goričar
authors.affiliation: a Department of Hematology and Oncology , University Children's Hospital , Ljubljana , Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
mesh_terms: D000293:Adolescent; D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018091:Receptors, AMPA / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase; D018091:Receptors, AMPA
keywords: Genetic and other predisposing conditions; allergy and hypersensitivity; lymphoid leukemia