Division of Medicinal Safety Science, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Division of Medicinal Safety Science, National Institute of Health Sciences, Setagaya, Tokyo, Japan; Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
J Pharm Sci. 2017 Sep;106(9):2914-2918. doi: 10.1016/j.xphs.2017.05.002. Epub 2017 May 8.
Lipid metabolites in the blood are expected to be biomarker candidates to reflect disease states and responses to therapeutic drugs. However, their profiles are influenced by subject background, which may lead to confounding results. This study aimed to evaluate whether age and gender affect lipid metabolite levels in the plasma of healthy Japanese adults. Comprehensive lipidomic analysis was performed using liquid chromatography-mass spectrometry for overnight fasted volunteers consisting of 4 groups of 15 subjects each: young males (25-35 years), elderly males (55-64 years), young females (25-35 years), and elderly females (55-65 years). Of 326 detected lipids, none showed significant gender-associated differences in the young groups and 3 metabolites showed significant gender-associated differences in the elderly groups, suggesting that age has little impact on plasma lipid levels in Japanese subjects. We found age-associated differences in 111 (34%) and 115 (35%) metabolites in males and females, respectively, indicating that the subjects' age should be considered an important confounding factor for lipid biomarker exploration and validation studies in Japanese populations. These findings provide fundamental information on biomarker discovery, validation, and qualification processes in Japanese populations, and facilitate the evaluation of biomarker candidates found in other populations.
血液中的脂质代谢物有望成为反映疾病状态和对治疗药物反应的生物标志物候选物。然而,它们的分布受到受试者背景的影响,这可能导致混杂结果。本研究旨在评估年龄和性别是否会影响日本健康成年人血浆中的脂质代谢物水平。使用液相色谱-质谱法对禁食过夜的志愿者进行了全面的脂质组学分析,志愿者分为 4 组,每组 15 人:年轻男性(25-35 岁)、老年男性(55-64 岁)、年轻女性(25-35 岁)和老年女性(55-65 岁)。在检测到的 326 种脂质中,年轻组中没有一种表现出与性别相关的显著差异,而老年组中有 3 种代谢物表现出与性别相关的显著差异,这表明年龄对日本受试者的血浆脂质水平影响不大。我们发现男性和女性分别有 111(34%)和 115(35%)种代谢物与年龄相关,这表明在日本人群中进行脂质生物标志物探索和验证研究时,受试者的年龄应被视为一个重要的混杂因素。这些发现为日本人群中的生物标志物发现、验证和资格认定过程提供了基础信息,并有助于评估其他人群中发现的生物标志物候选物。