• Peter Nagele, Barbara Zeugswetter, Corinna Eberle, Michael Hüpfl, Martina Mittlböck, and Manuela Födinger.
• Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA. nagelep@wustl.edu
• Pharmacogenet. Genomics. 2009 May 1;19(5):325-9.

ObjectivesOxidation 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.MethodsIn 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.ResultsNo 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.ConclusionIn 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.

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