HLA-DRB1*16:02 is associated with PEG-asparaginase hypersensitivity

Pharmacogenomics. 2021 Nov;22(17):1135-1142. doi: 10.2217/pgs-2021-0107. Epub 2021 Nov 8.

Abstract

Aim: To evaluate the associations between human leukocyte antigen (HLA)-DRB1 variants and the rs6021191 variant in nuclear factor of activated T cells 2 (NFATC2) with PEG-asparaginase hypersensitivity in children with acute lymphoblastic leukemia (ALL) treated according to the Chinese Children Leukemia Group (CCLG) ALL 2018 protocol. Methods:HLA-DRB1 genotyping was performed using a PCR sequence-based typing (SBT) method. NFATC2 rs6021191 was genotyped applying TaqMan Genotyping Assay. Results: T-ALL and higher risk groups were at higher risk for PEG-asparaginase hypersensitivity. No association was found between NFATC2 rs6021191 and PEG-asparaginase hypersensitivity. HLA-DRB1*16:02 variant was associated with PEG-asparaginase allergy both in univariate and multivariate logistic regression analysis. Conclusion: Our results confirm that variations in HLA-DRB1 might influence the development of asparaginase hypersensitivity.

Keywords: HLA-DRB1*16:02; NFATC2; PEG-asparaginase; hypersensitivity; pediatric acute lymphoblastic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asparaginase / adverse effects*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / genetics
  • Female
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Infant
  • Male
  • NFATC Transcription Factors / genetics
  • Polyethylene Glycols / adverse effects*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*

Substances

  • HLA-DRB1 Chains
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase