Related Experiment Video
Updated: Jun 24, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
A common gene variant in methionine synthase reductase is not associated with peak homocysteine concentrations after
Peter Nagele1, Barbara Zeugswetter, Corinna Eberle
1Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA. nagelep@wustl.edu
Objectives:
Oxidation of vitamin B12 by nitrous oxide leads to the inactivation of methionine synthase resulting in elevated plasma total homocysteine concentrations. Methionine synthase reductase is the only human enzyme that is able to reverse the oxidation of vitamin B12, which also occurs naturally by reactive oxygen species. A common polymorphism in methionine synthase reductase, MTRR 66A>G, is associated with reduced enzyme activity. Thus, we hypothesized that patients with this gene variant develop higher plasma total homocysteine concentrations after nitrous oxide anesthesia than wild-type patients.
Methods:
In this follow-up investigation of a previous gene association study, we prospectively included 140 healthy individuals undergoing elective surgery under general anesthesia that included 66% nitrous oxide. Peak postoperative plasma total homocysteine was the main outcome variable and was measured within 2 h after the end of anesthesia. The MTRR 66A>G genotype was determined after completion of the study. The association between genotype and peak postoperative total homocysteine was modeled with a general linear model.
Results:
No association between MTRR 66A>G and immediate postoperative plasma total homocysteine after nitrous oxide anesthesia was detected. All three groups, stratified by genotype (MTRR 66AA, AG, GG), shared similar baseline characteristics and increases in plasma total homocysteine. The average increase in plasma homocysteine was 2.4 mumol/l (+28%) in all three groups indicating the expected inactivation of methionine synthase by nitrous oxide through oxidation of vitamin B12, but no genetic effect.
Conclusion:
In conclusion, this study showed that the MTRR 66A>G gene variant is not associated with peak elevated postoperative plasma total homocysteine after nitrous oxide anesthesia. Whether the gene influences the rate of recovery of methionine synthase remains to be determined.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
01:17Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life