|| Typical BuChE
|| Heterozygous for "atypical" BuChE
|| Homozygous for "atypical" BuChE; see warning re drug (incl. anesthetic) use
|?|| (A;A) (A;G) (G;G) ||28|
, also known as D70G, is a SNP in the BCHE
gene. This SNP affects the structure, activity, and substrate specificity of the BuChE (butyrylcholinesterase) enzyme.
[Cholinesterases and cholinesterase inhibitors, p. 48] The variant form, rs1799807(G), replaces aspartate with glycine at the secondary substrate/inhibitor binding site. This single base substitution yields the "atypical" version of BChE. This version has a lower affinity for many substrates, including many Cholinesterase Inhibitors (CIs). A different cholinesterase (acetylcholinesterase, AChE) is an important component of neurotransmission by acetylcholine (ACh), terminating the action of ACh after it has been released during neurotransmission. BChE is found widely in the plasma and normally binds to CIs, protecting AChE from being inhibited by CIs and so maintaining normal neurotransmission by acetylcholine.
Practical consequences of altered substrate affinity from this SNP include:
- Succinylcholine, commonly used as an anesthetic, depends on BChE hydrolysis for recovery. rs1799807(G;G) homozygotes experience a much delayed return to spontaneous breathing following its use.
- "Atypical" BChE has a low affinity for CI alkaloids naturally occuring in certain plants, particularly those in the nightshade family (potato, tomato, peppers, eggplant, etc.). rs1799807(G) carriers may be more prone to physiological consequences of AChE inhibition from eating these foods.
- Many pesticides are CIs, including organophosphates and carbamates. rs1799807(G) carriers may have atypical reactions to pesticide residues on foods and in the environment.
- Many nerve agents, such as Sarin and VX gas, as well agents used to protect soldiers against them, such as pyridostigmine, are CIs. rs1799807(G) carriers may be more susceptible to exposure to these agents.
[PMID 15060281] "Atypical" BuChE, rs1799807(G), has 30% lower enzymatic activity than the wild-type enzyme. Homoygous carriers of this polymorphism, rs1799807(G;G), display extreme anxiety after exposure to CIs.
|| Moderate clinical importance, pathogenic
|| A well-established recessive variant causing "Butyrylcholinesterase deficiency" or "pseudocholinesterase deficiency". According to Yen, et al. this is the most well-studied variant causing that deficiency. This causes increased sensitivity to choline esters and certain other drugs.