Genetic Variations in GRIA1 on Chromosome 5q33 Related to Asparaginase Hypersensitivity

被引：66

作者：

Chen, S-H ^{[1
,2
]}

Pei, D. ^{[3
]}

Yang, W. ^{[1
]}

Cheng, C. ^{[3
]}

Jeha, S. ^{[4
]}

Cox, N. J. ^{[5
]}

Evans, W. E. ^{[1
,6
,7
]}

Pui, C-H ^{[4
,6
,7
]}

Relling, M. V. ^{[1
,6
,7
]}

机构：

[1] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[2] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Div Hematol Oncol,Dept Pediat, Tao Yuan, Taiwan

[3] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA

[4] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA

[5] Univ Chicago, Div Human Genet, Dept Biol Sci, Chicago, IL 60637 USA

[6] Univ Tennessee, Coll Med, Memphis, TN USA

[7] Univ Tennessee, Coll Pharm, Memphis, TN USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2010年 / 88卷 / 02期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; COLI L-ASPARAGINASE; GENOME-WIDE SEARCH; ESCHERICHIA-COLI; ABACAVIR HYPERSENSITIVITY; CHILDHOOD ASTHMA; ASSOCIATION; POPULATIONS; CHILDREN; HLA-B-ASTERISK-5701;

D O I：

10.1038/clpt.2010.94

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (rs4958381), 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.

引用

页码：191 / 196

页数：6

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