Weng Liming, Quinlivan Eoin, Gong Yan, Beitelshees Amber L, Shahin Mohamed H, Turner Stephen T, Chapman Arlene B, Gums John G, Johnson Julie A, Frye Reginald F, Garrett Timothy J, Cooper-DeHoff Rhonda M
1 Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida , College of Pharmacy, Gainesville, Florida.
Metab Syndr Relat Disord. 2015 Jun;13(5):195-202. doi: 10.1089/met.2014.0132. Epub 2015 Feb 9.
The three branched amino acids (valine, leucine, and isoleucine) and two aromatic amino acids (tyrosine and phenylalanine) have been associated with many adverse metabolic pathways, including diabetes. However, these associations have been identified primarily in otherwise healthy Caucasian populations. We aimed to investigate the association of this five-amino-acid signature with metabolic syndrome and impaired fasting glucose (IFG) in a hypertensive cohort of Caucasian and African Americans.
We analyzed data from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies PEAR and PEAR2 conducted between 2005 and 2014. Subjects were enrolled at the University of Florida (Gainesville, FL), Emory University (Atlanta, GA), and Mayo Clinic (Rochester, MN). A total of 898 patients with essential hypertension were included in this study. Presence of metabolic syndrome and IFG at baseline were determined on the basis of measurements of demographic and biochemical data. Levels of the five amino acids were quantified by liquid chromatography-tandem mass spectroscopy (LC-MS/MS).
With a multiple logistic regression model, we found that all five amino acids were significantly associated with metabolic syndrome in both Caucasian and African Americans. IFG and the five amino acids were associated in the Caucasian Americans. Only valine was significantly associated with IFG in African Americans.
In both Caucasian and African Americans with uncomplicated hypertension, plasma levels of the five-amino-acid signature are associated with metabolic syndrome. Additionally, in Caucasians we have confirmed the five-amino-acid signature was associated with IFG.
三种支链氨基酸(缬氨酸、亮氨酸和异亮氨酸)以及两种芳香族氨基酸(酪氨酸和苯丙氨酸)与包括糖尿病在内的许多不良代谢途径有关。然而,这些关联主要是在其他方面健康的白种人群体中发现的。我们旨在研究这五种氨基酸特征与白种人和非裔美国人高血压队列中的代谢综合征及空腹血糖受损(IFG)之间的关联。
我们分析了2005年至2014年间进行的抗高血压反应药物基因组学评估(PEAR)研究PEAR和PEAR2的数据。研究对象在佛罗里达大学(佛罗里达州盖恩斯维尔)、埃默里大学(佐治亚州亚特兰大)和梅奥诊所(明尼苏达州罗切斯特)招募。本研究共纳入898例原发性高血压患者。根据人口统计学和生化数据测量结果确定基线时代谢综合征和IFG的存在情况。通过液相色谱 - 串联质谱法(LC-MS/MS)对这五种氨基酸的水平进行定量。
通过多元逻辑回归模型,我们发现这五种氨基酸在白种人和非裔美国人中均与代谢综合征显著相关。IFG与这五种氨基酸在白种美国人中有关联。在非裔美国人中,只有缬氨酸与IFG显著相关。
在患有单纯性高血压的白种人和非裔美国人中,这五种氨基酸特征的血浆水平均与代谢综合征有关。此外,在白种人中,我们证实了这五种氨基酸特征与IFG有关。