BCHE rs28933390: Anesthesia Sensitivity and Apnea Risk
The genetic variant rs28933390 is a rare missense variation located in the butyrylcholinesterase (BCHE) gene. It corresponds to the classic fluoride-resistant allele (F2 or Fluoride-2), which produces an enzyme with reduced hydrolytic efficiency toward certain short-acting muscle relaxants. Carriers of this variant face an increased risk of prolonged post-anesthesia apnea when administered neuromuscular blocking agents like succinylcholine or mivacurium.
What each genotype means
Typical enzyme activity
This genotype represents the most common form of the BCHE gene, which is typically associated with normal butyrylcholinesterase enzyme function. Individuals with this genotype are expected to metabolize medications like succinylcholine and mivacurium at standard rates. Please discuss any upcoming surgical procedures or anesthesia requirements with your clinician or anesthesiologist.
This is the most common genotype found globally, as the variant allele is extremely rare.
Reduced enzyme activity risk
This genotype indicates you carry one copy of the F2 (fluoride-resistant) variant, which is associated with reduced butyrylcholinesterase enzyme activity. This may lead to impaired breakdown of certain muscle relaxants, potentially increasing the risk of prolonged apnea after anesthesia. Please inform your healthcare provider or anesthesiologist of this genetic finding before any surgery.
This genotype is extremely rare, with a minor allele frequency of less than 0.001 globally.
Increased apnea risk
This genotype indicates you carry two copies of the F2 variant, which is strongly associated with significantly impaired butyrylcholinesterase enzyme activity. You may be at a higher risk for prolonged apnea when exposed to medications like succinylcholine or mivacurium. It is essential to share this information with your medical team and anesthesiologist to ensure appropriate clinical management.
This genotype is exceptionally rare in the general population.
Molecular Identity and Genomic Location
The single nucleotide polymorphism rs28933390 resides within the coding sequence of the BCHE gene located on chromosome 3. In biochemical literature, this variant is classically characterized by a transversion that causes an amino acid substitution, often designated as Gly390Val or Gly418Arg depending on whether the mature protein sequence or the full precursor polypeptide containing the signal peptide is indexed. This alteration defines the BCHE fluoride-resistant 2 (F2) allele. In laboratory assays, the resulting butyrylcholinesterase enzyme demonstrates resistance to inhibition by sodium fluoride, a defining in vitro characteristic distinguishing it from standard wild-type cholinesterase and other atypical enzyme forms.
The Biological Role of Butyrylcholinesterase
The BCHE gene encodes butyrylcholinesterase, also referred to as pseudocholinesterase or plasma cholinesterase. Primarily synthesized in the liver and secreted directly into circulation, this enzyme is responsible for metabolizing ester-containing compounds, including dietary toxins, organophosphate pesticides, and specific pharmacological agents. Under routine clinical circumstances, butyrylcholinesterase rapidly breaks down depolarizing and non-depolarizing neuromuscular blockers such as succinylcholine and mivacurium. Because these medications temporarily paralyze skeletal muscles to facilitate endotracheal intubation and mechanical ventilation during surgery, prompt plasma enzymatic clearance is essential to restore spontaneous breathing within three to five minutes following administration.
Pharmacogenomic Impact and Apnea Risk
When an individual carries functional variants in the BCHE gene, the plasma clearance of succinylcholine or mivacurium can be dramatically diminished. For individuals who carry rs28933390—particularly as homozygotes or in compound heterozygosity with other disabling variants such as the atypical A-variant (rs1799807) or silent null alleles—neuromuscular blockade is significantly lengthened. Instead of the typical rapid recovery, affected individuals can experience prolonged post-anesthetic apnea lasting anywhere from thirty minutes to several hours. The clinical evidence linking rs28933390 to impaired drug breakdown is biologically well-established, though published clinical data remains categorized as limited primarily because the allele is extraordinarily rare in global sequencing datasets compared to more prevalent variants.
Population Frequency and Clinical Inheritance
The rs28933390 variant is exceptionally rare across worldwide populations, exhibiting an overall minor allele frequency of less than 0.001 (below 0.1%). Hereditary pseudocholinesterase deficiency operates primarily under an autosomal recessive inheritance model. Heterozygous carriers harboring a single altered allele generally retain sufficient baseline enzyme function to avoid severe complications, although they may occasionally experience modest delays in drug clearance. Markedly prolonged apnea almost universally requires two altered alleles—either two copies of a fluoride-resistant allele or one fluoride-resistant allele paired with an atypical or silent BCHE allele.
What Readers Can and Cannot Do With This Result
Knowledge of carrying rs28933390 cannot be used as a standalone medical diagnosis, nor does it imply any adverse day-to-day health symptoms, as pseudocholinesterase deficiency is otherwise entirely benign. However, this pharmacogenomic information is profoundly valuable prior to elective procedures involving general anesthesia. If you carry this variant or have a family history of extended recovery from surgical muscle relaxants, you should share your genetic results and medical history with your clinician, surgical team, and anesthesiologist. Anesthesia providers can readily substitute alternative neuromuscular blockers that do not rely on butyrylcholinesterase clearance, completely eliminating the risk of unexpected prolonged paralysis.
How common is this variant?
The rs28933390 variant is extremely rare globally, with an observed minor allele frequency of less than 0.001 across all major continental ancestries in population cohorts such as gnomAD.
Frequently asked questions
What is the primary risk associated with rs28933390?
The primary clinical risk is prolonged post-anesthetic apnea. If given specific muscle relaxants such as succinylcholine or mivacurium during surgery, individuals with reduced butyrylcholinesterase activity may remain paralyzed and unable to breathe spontaneously for an extended duration, requiring continued mechanical ventilation until the drug slowly clears.
Does having this variant cause everyday health problems?
No, butyrylcholinesterase deficiency does not cause chronic physical symptoms, pain, or illness in routine life. The condition is clinically silent and typically only manifests as a problem when specific medications or particular agricultural chemical toxins enter the bloodstream.
How can anesthesiologists manage this genetic variant?
Anesthesiologists frequently utilize alternative muscle relaxants that do not rely on butyrylcholinesterase for clearance, such as rocuronium or vecuronium, which have dedicated reversal agents. Informing your surgical care team about your genetic status ahead of time allows them to select safe, alternative agents and avoid prolonged paralysis entirely.
Can acquired medical conditions also affect BCHE enzyme levels?
Yes, acquired factors can lower butyrylcholinesterase activity independently of genetics. Severe liver disease, malnutrition, chronic kidney failure, pregnancy, severe burns, and certain concurrent medications can temporarily reduce circulating enzyme levels and extend drug clearance times.
Sources & further reading
Educational information only, last refreshed 9/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A variant in the BCHE gene associated with butyrylcholinesterase activity levels.
Encodes the atypical A variant (Asp70Gly) of butyrylcholinesterase which drastically prolongs muscle paralysis after standard doses of mivacurium or succinylcholine.
Defines the BCHE atypical (A) variant (p.Asp70Gly) that causes prolonged paralysis and apnea following exposure to neuromuscular blockers such as succinylcholine or mivacurium.
Defines the BCHE fluoride-resistant (F1, p.Thr267Met) allele linked to reduced pseudocholinesterase activity and delayed recovery from succinylcholine-induced muscle relaxation.
Commonly known as the BCHE atypical variant (Asp70Gly), this single nucleotide change reduces pseudocholinesterase enzyme activity, affecting drug metabolism in obstetric anesthesia and reproduction-related surgical procedures.