Folate and homocysteine phenotypes: Comparative findings using research and clinical laboratory data
Folate and homocysteine phenotypes: Comparative findings using research and clinical laboratory data
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DOI：
10.1016/j.clinbiochem.2009.04.014
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发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Whitehead, Alexander S.
中科院分区：
文献类型：
--
作者：
Mitchell, Laura E.;Morales, Megan;Whitehead, Alexander S.
目的：低叶酸/高同型半胱氨酸表型与多种病理相关，包括脊柱裂和心血管疾病。叶酸和总同型半胱氨酸 (tHcy) 测量在临床上用于评估风险和补充叶酸的需求，并在研究中用于调查疾病的代谢基础。红细胞 (RBC) 叶酸是长期叶酸状态的最佳指标，通常以“总”叶酸来测量。然而，不同的叶酸衍生物支持不同的生化功能，这表明需要开发更精确的方法。本研究旨在评估基于稳定同位素稀释液相色谱-多反应监测/质谱 (LC-MRMNS) 的方法。设计和方法：我们使用 LC-MRM/MS 来定量 RBC 叶酸衍生物 5-甲基四氢叶酸 (5-CH3-THF)、四氢叶酸 (THF) 和 5,10-次甲基四氢叶酸 (5,10-methenylTHF)。绝经前妇女。评估每种叶酸衍生物的浓度在预测 tHcy 水平方面的实用性，并与常规临床实验室方法得出的叶酸和 tHcy 测量结果进行比较。结果：LC-MRM/MS 在确定叶酸和 tHcy 浓度方面在定性和定量上优于常规临床实验室方法。 RBC 5-CH3-THF 与 tHcy 具有相互关系（p=0.0003），而 RBC THF 和 RBC 5,10-methenylTHF 具有直接关系（分别为 p=0.01、0.04）。综合起来，这三个变量占 tHcy 变异的 42%。 结论：测量 RBC 5-CH3-THF 的稳健方法将提高叶酸/同型半胱氨酸表型分析在患者管理中的效用。 LC-MRM/MS 的使用将允许对高同型半胱氨酸血症和与低叶酸/高同型半胱氨酸表型相关的疾病进行研究，测量误差更小，统计能力更强，生成的数据有可能阐明复杂疾病和性状的病因机制。 (C) 2009 年加拿大临床化学家协会。由爱思唯尔公司出版。保留所有权利。
Objectives: A low folate/high homocysteine phenotype is associated with several pathologies, including spina bifida and cardiovascular disease. Folate and total homocysteine (tHcy) measurements are used clinically to assess risk and the need for folic acid supplementation and in research to investigate the metabolic basis of disease. Red blood cell (RBC) folate, the best indicator of long-term folate status, is usually measured as "total" folate. However, different folate derivatives support distinct biochemical functions, suggesting a need to develop more precise methods. This study was designed to evaluate a method based on stable isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRMNS).Design and methods: We used LC-MRM/MS to quantify the RBC folate derivatives 5-methyltetrahydrofolate (5-CH3-THF), tetrahydrofolate (THF), and 5,10-methenyltetrahydrofolate (5,10-methenylTHF) in pre-menopausal women. The concentration of each folate derivative was assessed for utility in predicting tHcy levels, and compared to folate and tHcy measurements derived by routine clinical laboratory methods.Results: LC-MRM/MS was qualitatively and quantitatively superior to routine clinical laboratory methods for determining folate and tHcy concentrations. RBC 5-CH3-THF had a reciprocal relationship with tHcy (p=0.0003), whereas RBC THF and RBC 5,10-methenylTHF had direct relationships.(p=0.01, 0.04 respectively). In combination, these three variables accounted for 42% of the variation in tHcy.Conclusions: Robust methods for measuring RBC 5-CH3-THF would improve the utility of folate/homocysteine phenotyping in patient management. The use of LC-MRM/MS Would allow studies of hyperhomocysteinemia and diseases associated with a low folate/high homocysteine phenotype to be performed with less measurement error and greater statistical power to generate data with the potential to elucidate the etiologic mechanisms of complex diseases and traits. (C) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.