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Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies

The Pharmacogenomics Journal volume 19, pages 305–314 (2019)Cite this article

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Abstract

Phenotypic rather than genotypic tests remain the gold standard for diagnosing glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, with increasing use of genomic arrays and whole exome or genome sequencing, G6PD genetic data are increasingly available. We examined the utility of G6PD genetic data in patients with hematologic malignancies and the association of G6PD genotype and phenotype with rasburicase-induced methemoglobinemia. We analyzed G6PD activity for 990 patients. Genotype data were available from the Affymetrix DMET array (n = 379), whole exome sequencing (n = 374), and/or the Illumina exome array (n = 634) for 645 patients. Medical records of 341 patients with methemoglobin measures were assessed for the administration of rasburicase. We observed 5 non-synonymous SNPs, 4 of which were known to be associated with deficient G6PD activity (WHO Class I–III). Genotyping 367 males resulted in a positive predictive value of 81.8% (47.8–96.8%), and two males with a Class I-III allele having normal activity both received a red blood cell transfusion prior to the activity assay. However, genotyping males had only 39.1% (20.5–61.2%) sensitivity. Two of the 12 heterozygous females had deficient G6PD activity. Rasburicase-induced methemoglobinemia occurred in 6 patients, 5 of whom had at least one Class I–III allele, despite 2 of these having normal G6PD activity. We conclude that although an apparent nondeficient genotype does not necessarily imply a normal phenotype, a deficient genotype result indicates a deficient phenotype in those without transfusions, and may be a useful adjuct to phenotype to prevent adverse drug reactions.

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Acknowledgements

This study was supported by grants GM 115279 and CA 21765

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Katherine M. Robinson, Wenjian Yang, Cyrine E. Haidar, Nancy Kornegay & Mary V. Relling

  2. Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jane S. Hankins

  3. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Dennis W. Jay

  4. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jeffrey E. Rubnitz, Ching-Hon Pui & Sima Jeha

  5. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Ulrich Broeckel

  6. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Cheng Cheng

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Robinson, K.M., Yang, W., Haidar, C.E. et al. Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies. Pharmacogenomics J 19, 305–314 (2019). https://doi.org/10.1038/s41397-018-0043-3

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