Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity.

Abstract	The genetic variations that result in allergy to asparaginase are as yet undetermined. We interrogated more than 500,000 single-nucleotide polymorphisms (SNPs) in 485 children with acute lymphoblastic leukemia (ALL), 322 in a discovery cohort, and 163 in a validation cohort. In the top 100 SNPs associated with allergy in the discovery cohort, chromosome 5 was overrepresented as compared with other chromosomes (P = 0.00032), hosting 10 SNPs annotated to genes. Among these 10 SNPs, one SNP (rs4958351) [corrected], in GRIA1 on chromosome 5q33, was replicated in the validation cohort (P = 1.8 x 10(-5), 2.9 x 10(-3), and 3.5 x 10(-7) in the discovery, validation, and combined cohorts, respectively). Four additional SNPs annotated to GRIA1 were also significantly associated with allergy (P < 0.05) in both cohorts. Chromosome 5q33 has previously been associated with asthma and atopy. These data contribute to the growing body of evidence that there is an inherited component to predisposition to drug allergy.
Authors	S-H Chen, D Pei, W Yang, C Cheng, S Jeha, N J Cox, W E Evans, C-H Pui, M V Relling
Journal	Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 88 Issue 2 Pg. 191-6 (Aug 2010) ISSN: 1532-6535 [Electronic] United States
PMID	20592726 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Receptors, AMPA DNA Asparaginase glutamate receptor ionotropic, AMPA 1
Topics	Adolescent Alleles Antineoplastic Agents (adverse effects, therapeutic use) Asparaginase (adverse effects, therapeutic use) Child, Preschool Chromosomes, Human, Pair 5 (genetics) Cohort Studies DNA (genetics) Drug Hypersensitivity (genetics) Female Genetic Predisposition to Disease Genetic Variation (genetics) Genome-Wide Association Study Genotype Humans Male Micronucleus, Germline Polymorphism, Single Nucleotide (genetics) Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (complications, drug therapy, genetics) Receptors, AMPA (genetics) Reproducibility of Results Risk

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