Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to...

Area of Science:

• Pharmacogenetics
• Anesthesiology
• Biochemistry

Background:

• Genetic variants in the butyrylcholinesterase (BCHE) gene are linked to reduced enzyme activity.
• This reduction can cause prolonged neuromuscular blockade after succinylcholine administration, leading to respiratory complications.
• Current BCHE deficiency testing is typically reserved for patients with a history of adverse reactions.

Purpose of the Study:

• To investigate the frequencies of BCHE genotypes associated with an increased risk of prolonged post-succinylcholine neuromuscular blockade.
• To assess the prevalence of BCHE variants in a large, multi-ethnic US population.

Main Methods:

• Genotyping of five key BCHE variants (A, K, F1, F2, S1) in 13,301 individuals undergoing routine pharmacogenetic testing.
• Stratification of BCHE genotypes into four phenotypic categories based on biochemical and clinical data to estimate risk.

Main Results:

• Minor allele frequencies for BCHE variants A, K, F1, F2, and S1 were 1.60%, 19.93%, 0.08%, 0.47%, and 0.04%, respectively.
• An estimated 0.06% of patients had severe BCHE deficiency, 8% had moderate deficiency, and 29% had mild deficiency.
• Caucasians exhibited a higher predicted frequency of BCHE deficiency compared to other ethnic groups.

Conclusions:

• Severe BCHE deficiency is rare in the US, but moderate deficiency affects approximately 8% of the population.
• A significant portion of patients may be at risk for prolonged neuromuscular blockade.
• Preoperative genetic testing for BCHE variants could benefit a substantial number of patients.