Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine
| العنوان: | Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine |
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| المؤلفون: | Eric Dawson, Angela Huskey, Andria L Del Tredici, Guangdan Zhu, Ronald J. Gordon |
| المصدر: | Pharmacogenomics and Personalized Medicine. 13:405-414 |
| بيانات النشر: | Informa UK Limited, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Pharmacology, Neuromuscular Blockade, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Gastroenterology, Minor allele frequency, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, Molecular Medicine, Family history, business, Pharmacogenetics, Butyrylcholinesterase, Depression (differential diagnoses), Genetic testing |
| الوصف: | Background 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. |
| تدمد: | 1178-7066 2893-3389 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::356e4165b1ca1c30ec2077f13ca40532Test https://doi.org/10.2147/pgpm.s263741Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........356e4165b1ca1c30ec2077f13ca40532 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 11787066 28933389 |
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