Table of Contents > Genomics > Butyrylcholinesterase gene polymorphism Print

Butyrylcholinesterase gene polymorphism


Related terms
Future research
Author information

Related Terms
  • BChE, butyrylcholinesterase, dibucaine number, DN, fluoride number, FN, genotype, molecular genetics, PCR, pharmacogenomics, phenotype, polymerase chain reaction polymorphism, pseudocholinesterase, variant.

  • Butyrylcholinesterase (BChE), also called pseudocholinesterase, is a protein in the blood that breaks down some types of drugs in a process called metabolism. Metabolism refers to the way the human body interacts with drugs, food, and any other ingested substance. Metabolism involves absorption in the digestive tract, processing in the liver and other organs, action of the substance within the cells, and elimination in the urine or stool.
  • Genes are found inside the nucleus of the cells of all organisms. An individual's genes are contained in a large molecule called DNA (deoxyribonucleic acid), which looks like a twisted ladder. This unique shape is called a double helix. The sides of the double helix are made of alternating sugar and phosphate molecules. The "rungs of the ladder" are made of small molecules called bases. These molecules include adenine (A), thymine (T), cytosine (C), and guanine (G). The pattern of these bases determines which protein is made from a given gene.
  • Individuals may have slight differences in their DNA. If these differences are present in a gene, they are called alleles, or polymorphisms. Differences in alleles may result in genes that create proteins with more or less activity than others.
  • Some individuals have BChE gene polymorphisms, or variants, that cause the BChE protein to be less active than normal. People with these variants are said to have pseudocholinesterase deficiency. People with pseudocholinesterase deficiency metabolize drugs more slowly so that the drug remains in their bodies for longer periods of time. They may therefore react more strongly and for a longer period of time than normal to a specific dose of a drug, which means they also have a higher risk of severe side effects.
  • BChE metabolizes drugs called choline esters. Some examples of these drugs include succinylcholine and cocaine. Succinylcholine is used during surgery to temporarily paralyze the muscles of the body. In normal individuals, its effects last for five minutes. In patients with pseudocholinesterase deficiency, succinylcholine is metabolized much more slowly, and the muscle paralysis may last much longer, up to eight hours. Cocaine is a narcotic drug of abuse. Cocaine may cause sudden death in people with pseudocholinesterase deficiency. This is because they cannot metabolize the drug and accumulate extremely high levels in the body.
  • Pseudocholinesterase deficiency is most common in people of European descent. It is rare in Asians. In a European study, 1.3% of participants had pseudocholinesterase deficiency. A community in India called Arya Vysya has a very high rate of the disorder.

  • Enzymatic assay: Enzyme activity is the method used to diagnose pseudocholinesterase deficiency. A blood sample is taken from the patient, and a molecule that is metabolized by BChE is added to the blood, along with an indicator chemical that changes color when BChE is actively metabolizing the molecule. The activity of BChE is measured by determining the amount of color change in the blood. Low levels of BChE will result in a very slight or no color change.
  • Dibucaine number and fluoride number: Some polymorphisms, called gene variants, react differently in laboratory tests. Polymorphisms of the BChE gene cause the protein to be less active. These variants are detected by the addition of the chemicals dibucaine or fluoride to the blood sample, which blocks the reaction of BChE in the blood.
  • Dibucaine and fluoride are used to test the activity of BChE in the blood. The percentage of the protein that is blocked by dibucaine is called the dibucaine number (DN). Normal individuals have a DN of 80% or higher. Patients with a specific polymorphism in the BChE gene have a DN of 20% or lower. The percentage of the protein that is blocked by fluoride is called the fluoride number (FN). Patients with an FN of about 36% or less have decreased activity of the BChE protein.
  • Polymerase chain reaction (PCR): Polymerase chain reaction (PCR) is currently used in research and in specialized labs to detect gene variants associated with pseudocholinesterase deficiency. A small sample of cells is taken from a tumor that has been surgically removed, a blood sample, or a swab of the inside of the mouth. The genetic material is copied hundreds of times to create a larger sample. Molecules called "probes," which are DNA segments specifically designed to attach to a specific allele, are then used to tag the gene and identify it. Probes can be used to identify gene variants and to determine the amount of variant gene present in the cell.
  • DNA sequencing: DNA sequencing is a method of determining the exact pattern of adenine (A), guanine (G), cytosine (C), and thymine (T) in a DNA fragment. These DNA molecules determine which protein is made from a gene. In the gene for BChE, changes in the pattern of these molecules results in a slightly different protein that may be more or less active. To sequence DNA, the segment is mixed with an enzyme that copies the DNA, a primer (a segment of DNA that tells the enzyme where to begin copying), and the four nitrogen bases (A, G, C, and T) required to synthesize DNA.
  • DNA sequencing may be used in research to study a new polymorphism and determine its exact structure. By knowing its structure, researchers may be able to determine what effect it has in the body.

  • Pharmacogenomics is the study of how an individual's genetic makeup affects their response to drugs. Some patients respond differently to drugs from others. For instance, one patient may require a very high dose of a certain medication to have an effect, while another patient may have major side effects from a small dose. Pharmacogenomics includes the study of both pharmacokinetics and pharmacodynamics. Pharmacokinetics is the metabolism of drugs in the body by proteins in the liver, blood, and other organs. Pharmacodynamics is the interaction of drugs within cells to treat a disease.
  • BChE is not currently being researched heavily. Areas that are being evaluated are the use of pre-surgical testing for BChE to determine which patients are most likely to have adverse effects to drugs used during surgery, such as succinylcholine.

  • Individuals have 46 chromosomes consisting of 22 pairs of autosomes and one pair of sex chromosomes. BChE or pseudocholinesterase deficiency may be inherited in an autosomal fashion, meaning that the defective gene is located on one of the autosomes. There are several different alleles that may be inherited, and affected individuals may inherit one or two defective alleles. If a patient has a family member with the deficiency, it may be useful to be tested.
  • Patients diagnosed with pseudocholinesterase deficiency are treated with different drugs from the usual drugs when they undergo anesthesia for surgery. Any patient with a history of pseudocholinesterase deficiency should tell his or her doctor to avoid potentially serious adverse effects.

  • Because pseudocholinesterase deficiency is rare, it is not tested for prior to surgery. This means that most patients are not diagnosed until they have an adverse reaction to medication during surgery, or unless they have a family history of the disorder.


Future research
  • Future research into the prevalence of pseudocholinesterase deficiency among specific racial and ethnic groups may allow for testing to be performed in patients that are at high risk. This means that patients who are more likely to have the disorder can be tested prior to having surgery so that a different drug can be used, such as pancuronium and vecuronium.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (

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