亚甲基四氢叶酸还原酶基因多态性对氧化亚氮麻醉后同型半胱氨酸浓度的影响。

Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia.

作者信息

Nagele Peter, Zeugswetter Barbara, Wiener Caspar, Burger Hansjörg, Hüpfl Michael, Mittlböck Martina, Födinger Manuela

机构信息

Department of Anesthesiology, Critical Care Medicine and Pain Therapy, Medical University of Vienna, Vienna, Austria.

出版信息

Anesthesiology. 2008 Jul;109(1):36-43. doi: 10.1097/ALN.0b013e318178820b.

DOI:10.1097/ALN.0b013e318178820b

PMID:18580170

Abstract

BACKGROUND

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene (677C>T, 1298A>C) cause elevated plasma homocysteine concentrations and have been linked to fatal outcomes after nitrous oxide anesthesia. This study tested the hypothesis that patients with common MTHFR 677C>T or 1298A>C mutations develop higher plasma homocysteine concentrations after nitrous oxide anesthesia than wild-type patients.

METHODS

In this prospective, observational cohort study with blinded, mendelian randomization, the authors included 140 healthy patients undergoing elective surgery. All patients received 66% nitrous oxide for at least 2 h. The main outcome variable, plasma total homocysteine, and folate, vitamin B12, and holotranscobalamin II were measured before, during, and after surgery. After completion of the study, all patients were tested for their MTHFR 677C>T or 1298A>C genotype.

RESULTS

Patients with a homozygous MTHFR 677C>T or 1298A>C mutation (n = 25) developed higher plasma homocysteine concentrations (median [interquartile range], 14.9 [10.0-26.4] microm) than wild-type or heterozygous patients (9.3 [7.5-15.5] microm; n = 115). The change in homocysteine after nitrous oxide anesthesia was tripled in homozygous patients compared with wild-type (5.6 microm [+60%] vs. 1.8 microm [+22%]). Only homozygous patients reached average homocysteine levels considered abnormal (> 15 microm). Plasma 5-methyl-tetrahydrofolate concentrations increased uniformly by 20% after nitrous oxide anesthesia, indicating the inactivation of methionine synthase and subsequent folate trapping. Holotranscobalamin II concentrations remained unchanged, indicating no effect of nitrous oxide on vitamin B12 plasma concentrations.

CONCLUSIONS

This study shows that patients with a homozygous MTHFR 677C>T or 1298A>C mutation are at a higher risk of developing abnormal plasma homocysteine concentrations after nitrous oxide anesthesia.

摘要

背景

亚甲基四氢叶酸还原酶（MTHFR）基因（677C>T、1298A>C）突变会导致血浆同型半胱氨酸浓度升高，并且与一氧化二氮麻醉后的致命后果有关。本研究检验了以下假设：与野生型患者相比，携带常见MTHFR 677C>T或1298A>C突变的患者在一氧化二氮麻醉后血浆同型半胱氨酸浓度会升得更高。

方法

在这项采用盲法孟德尔随机化的前瞻性观察性队列研究中，作者纳入了140例接受择期手术的健康患者。所有患者均接受66%的一氧化二氮，持续至少2小时。在手术前、手术期间和手术后测量主要结局变量血浆总同型半胱氨酸以及叶酸、维生素B12和全转钴胺素II。研究结束后，对所有患者进行MTHFR 677C>T或1298A>C基因型检测。

结果

纯合MTHFR 677C>T或1298A>C突变患者（n = 25）的血浆同型半胱氨酸浓度（中位数[四分位间距]，14.9[10.0 - 26.4]微摩尔）高于野生型或杂合子患者（9.3[7.5 - 15.5]微摩尔；n = 115）。与野生型相比，一氧化二氮麻醉后纯合患者同型半胱氨酸的变化增加了两倍（5.6微摩尔[增加60%]对1.8微摩尔[增加22%]）。只有纯合患者达到了被认为异常的平均同型半胱氨酸水平（> 15微摩尔）。一氧化二氮麻醉后血浆5 - 甲基四氢叶酸浓度均匀升高20%，表明甲硫氨酸合成酶失活以及随后的叶酸捕获。全转钴胺素II浓度保持不变，表明一氧化二氮对血浆维生素B12浓度没有影响。