Routine Screening of African American Males in Hematology Oncology Clinic for G6PD Deficiency: A Prospective Comparative Study of a Pharmacogenomic Panel Versus Standard Enzyme Assay
Authors: Sareen Srishti , Adabala Jaya , Stoops Katie , Marler Jacob , Lands Lindsey , Weir Alva 
Published: December 2024

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency can cause acute hemolytic anemia due to oxidative stress in red blood cells triggered by medications. This condition is highly prevalent among African American males (AAM), impacting drug response in hematologic malignancies. Phenotypic tests have long been the standard for diagnosing G6PD deficiency; however, the activity assay results are not always accurate and are influenced by various factors such as reticulocyte count, recent blood transfusion, anemia, sample handling, or temperature variations. Genetic testing could help avoid these false results that occur when measuring G6PD activity in blood. Currently, no studies have been done to compare the standard enzymatic assays and pharmacogenomics (PGx) panel for the G6PD population in adult AAM, particularly in Hematology and Oncology patients where drugs are often used that cause high oxidative stress. This study aims to investigate the sensitivity, clinical relevance, and cost-effectiveness of a PGx panel versus traditional enzyme assays for diagnosing G6PD deficiency in adult AAM in a Veteran Clinic. This study will also examine the clinical importance of identifying genetic polymorphisms in drug metabolizing enzymes of chemotherapy medications commonly used by our patients in our Hematology/Oncology Clinic.
Methods: This is a prospective study of AAM aged 18 or older attending the Hematology Oncology Clinic at Lt. Col. Luke Weathers, Jr. VA Medical Center in Memphis, TN. This study initially enrolled 92 participants, with plans to expand based on preliminary findings. Recruitment involved obtaining verbal consent from participants by the Principal Investigator (PI) and sub-investigators during clinic visits or via telephone, without the use of recruitment materials or incentives. Participants were tested with both a VA-funded 16-gene PGx panel (evaluating select genetic loci in: CYP2C, CYP2C9, CYP2C19, CYP2D6, DPYD, TPMT, CYP4F2, VKORC1, SLCO1B1, CYP3A5, UGT1A1, ABCG2, CYP2B6, G6PD, HLA-B*57:01, and NUDT15), and a standard G6PD enzyme assay. For the first phase of this study, data analysis focused on comparison of sensitivity, specificity, concordance and cost effectiveness of the tests, and the analysis of G6PD allele frequency and distribution. Clinical relevance for each G6PD positive patient was also determined.
Results: A total of 92 AAM participants were included in this quality improvement project. Among them, 15% (14 out of 92) were found to have G6PD deficiency. Of these 14 patients, 12 were diagnosed with G6PD deficiency through both enzyme assay and PGx panel. 1 patient had normal enzyme levels but was identified as deficient based on genotype, and another patient had a normal genotype but low enzyme levels. The A-202A_376G allele was predominantly responsible for the majority of low-function alleles in AAM population. Over the past 10 years, only 1 of the 14 patients showed signs of hemolysis. None of the patients with G6PD deficiency were taking any high- or intermediate-risk medications. Apart from G6PD, 37% of patients were found to have at least 1 genetic polymorphism from PGx testing in chemotherapy drug metabolizing enzymes with UGT1A1 being the most common.
Discussion: The prevalence of G6PD deficiency in our cohort of AAM patients (15%) is higher than that reported in the literature (10%). The G6PD gene is highly polymorphic, with about 200 known variant alleles. All our patients with G6PD deficiency based on genotype harbored A-202A_376G allele which accounts for the vast majority of low function alleles in AAM population based on previously reported literature. The concordance rate between the enzymatic and PGx tests was observed to be 97.8%, and the sensitivity and specificity of the two tests were similar. PGx testing resulted in a change in G6PD status in 1 patient in the small population tested in this study. Although enzymatic assays are cheaper compared to PGx panels (3$ vs 225$), much additional information is provided with PGx testing that could impact many other therapeutics for patients in a hematology/oncology clinic. Additional studies are being carried out with these patients under an IRB approved protocol to determine the clinical relevance of additional PGx findings with the VA PGx panel.