PMID- 34747637 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20220310 IS - 1744-8042 (Electronic) IS - 1462-2416 (Linking) VI - 22 IP - 17 DP - 2021 Nov TI - HLA-DRB1*16:02 is associated with PEG-asparaginase hypersensitivity. PG - 1135-1142 LID - 10.2217/pgs-2021-0107 [doi] AB - 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. FAU - Liu, Shuguang AU - Liu S AD - Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Gao, Chao AU - Gao C AD - Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Wu, Ying AU - Wu Y AD - Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Lin, Wei AU - Lin W AD - Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Li, Jun AU - Li J AD - Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Xue, Tianlin AU - Xue T AD - Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Wang, Linya AU - Wang L AD - Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Zheng, Huyong AU - Zheng H AD - Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. FAU - Zhang, Ruidong AU - Zhang R AD - Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211108 PL - England TA - Pharmacogenomics JT - Pharmacogenomics JID - 100897350 RN - 0 (HLA-DRB1 Chains) RN - 0 (NFATC Transcription Factors) RN - 0 (NFATC2 protein, human) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 7D96IR0PPM (pegaspargase) RN - EC 3.5.1.1 (Asparaginase) SB - IM MH - Adolescent MH - Asparaginase/*adverse effects MH - Child MH - Child, Preschool MH - Drug Hypersensitivity/*etiology/genetics MH - Female MH - Genotype MH - HLA-DRB1 Chains/*genetics MH - Humans MH - Infant MH - Male MH - NFATC Transcription Factors/genetics MH - Polyethylene Glycols/*adverse effects MH - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy OTO - NOTNLM OT - HLA-DRB1*16:02 OT - NFATC2 OT - PEG-asparaginase OT - hypersensitivity OT - pediatric acute lymphoblastic leukemia EDAT- 2021/11/09 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/11/08 12:14 PHST- 2021/11/09 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/11/08 12:14 [entrez] AID - 10.2217/pgs-2021-0107 [doi] PST - ppublish SO - Pharmacogenomics. 2021 Nov;22(17):1135-1142. doi: 10.2217/pgs-2021-0107. Epub 2021 Nov 8.