Blackwell S, O'Reilly D St J, Talwar D
Royal Infirmary, Glasgow, UK.
Eur J Clin Invest. 2007 May;37(5):364-71. doi: 10.1111/j.1365-2362.2007.01798.x.
Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase which is believed to be a cause of endothelial dysfunction and has been shown to predict the occurrence of acute coronary events. Data regarding the biological variation of arginine and its methylated derivatives are conspicuously absent from the literature. Such data are important in setting analytical quality specifications, assessing the utility of population reference intervals and assessing the significance of changes in serial results from an individual.
Arginine, homoarginine, ADMA and symmetric dimethylarginine (SDMA) are measured in plasma by high performance liquid chromatography. Twelve healthy volunteers underwent weekly blood sampling for 20 weeks in order to determine the intra- and inter-individual biological variation of these analytes, from which analytical quality specifications, indices of individuality (II) and reference change values (RCV) are derived. Plasma samples from 100 healthy individuals were obtained in order to determine population reference intervals.
ADMA and symmetric dimethylarginine (SDMA) exhibit low intra-individual biological variation of 7.4% and 5.8%, respectively, imposing desirable imprecision goals (CV(A)) of < or = 3.7% and 2.9% for these analytes. The described methodology achieves these goals, with analytical CVs of < 3.5% for all analytes. Goals for bias and total error were 3.1-10.1% and 7.2-16.0%, respectively. Reference intervals for ADMA and SDMA were 0.29-0.63 micromol L(-1) and 0.24-0.55 micromol L(-1), but have IIs < 1. RCVs were at least 20% for all analytes studied.
Dimethylarginine concentrations are tightly controlled in health, with the result that imprecision goals for laboratory methods require to be low. Relatively large differences are required between serial results to denote a significant change. Population reference intervals for dimethylarginines are likely to be of limited value in detecting 'abnormality' in an individual from a single result.
不对称二甲基精氨酸（ADMA）是一氧化氮合酶的内源性竞争性抑制剂，被认为是内皮功能障碍的一个原因，并且已被证明可预测急性冠状动脉事件的发生。文献中明显缺乏关于精氨酸及其甲基化衍生物生物学变异的数据。此类数据对于设定分析质量规范、评估人群参考区间的效用以及评估个体连续检测结果变化的意义非常重要。
采用高效液相色谱法测定血浆中的精氨酸、高精氨酸、ADMA和对称二甲基精氨酸（SDMA）。12名健康志愿者每周采血一次，共20周，以确定这些分析物的个体内和个体间生物学变异，由此得出分析质量规范、个体指数（II）和参考变化值（RCV）。采集100名健康个体的血浆样本以确定人群参考区间。
ADMA和对称二甲基精氨酸（SDMA）的个体内生物学变异较低，分别为7.4%和5.8%，这为这些分析物设定了理想的不精密度目标（CV(A)），即≤3.7%和2.9%。所描述的方法实现了这些目标，所有分析物的分析CV均<3.5%。偏差和总误差目标分别为3.1 - 10.1%和7.2 - 16.0%。ADMA和SDMA的参考区间分别为0.29 - 0.63 μmol L⁻¹和0.24 - 0.55 μmol L⁻¹，但个体指数<1。所有研究的分析物的参考变化值至少为20%。
健康状态下二甲基精氨酸浓度受到严格控制，因此实验室方法的不精密度目标需要较低。连续检测结果之间需要有相对较大的差异才能表明有显著变化。二甲基精氨酸的人群参考区间在通过单次检测结果检测个体“异常”方面可能价值有限。
