Pharmacogenomics and Personalized Medicine (Sep 2020)
Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine
Abstract
Guang-dan Zhu,1 Eric Dawson,1 Angela Huskey,1 Ronald J Gordon,2 Andria L Del Tredici1 1Millennium Health, LLC, San Diego, CA, USA; 2Department of Anesthesiology, University of California, UC San Diego School of Medicine, La Jolla, CA, USACorrespondence:Andria L Del TrediciMillennium Health, LLC, 16981 Via Tazon, San Diego, CA 92127, USATel +1 858 217 1175Fax +1 858 451 3636Email [email protected]: Genetic variants in the BCHE (butyrylcholinesterase) gene are associated with reduced BChE enzyme activity and prolonged post-succinylcholine neuromuscular blockade, which can lead to postanesthetic apnea and respiratory depression. Testing for BChE deficiency is usually performed by biochemical methods and is generally only offered to patients who have a personal or family history of prolonged post-succinylcholine neuromuscular blockade.Purpose: Using a clinical test, we investigated the frequencies of BCHE genotypes that are associated with increased risk for prolonged post-succinylcholine neuromuscular blockade.Materials and Methods: Five BCHE variants, including the A (atypical, rs1799807), K (Kalow, rs1803274), F1 (fluoride-1, rs28933389), F2 (fluoride-2, rs28933390), and S1 (silent-1, rs398124632), were genotyped in a large (n = 13,301), multi-ethnic cohort in the United States. Subjects were recipients of pharmacogenetic testing ordered by their physicians as part of routine care.Results: The minor allele frequencies of A, K, F1, F2, and S1 were 1.60%, 19.93%, 0.08%, 0.47%, and 0.04%, respectively, in this cohort. Based on a review of biochemical and clinical data of these variants, we grouped BCHE genotypes into four phenotypic categories to stratify the risk for prolonged post-succinylcholine neuromuscular blockade. Approximately 0.06% of patients were predicted to have severe BChE deficiency, 8% were predicted to have moderate BChE deficiency, and 29% were predicted to have mild BChE deficiency. Compared to other ethnic groups, Caucasians were predicted to have the highest frequency of BChE deficiency.Conclusion: While severe BChE deficiency is rare in the United States, approximately 8% of Americans are at moderate risk of prolonged post-succinylcholine neuromuscular blockade, suggesting that a sizable percentage of patients may benefit from preoperative genetic testing of BCHE.Keywords: succinylcholine, BCHE, genotyping, prolonged neuromuscular blockade, pharmacogenetics
