Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
Hypertension. 2013 Sep;62(3):621-6. doi: 10.1161/HYPERTENSIONAHA.113.01396. Epub 2013 Jun 24.
Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis, and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies, such as plasma lipidomic profiling, promise a better understanding of disorders in which there is a derangement of the lipid metabolism. However, association of plasma lipidomic profiles with hypertension in a high-risk population, such as Mexican Americans, has not been evaluated before. Using the rich data and sample resource from the ongoing San Antonio Family Heart Study, we conducted plasma lipidomic profiling by combining high-performance liquid chromatography with tandem mass spectroscopy to characterize 319 lipid species in 1192 individuals from 42 large and extended Mexican American families. Robust statistical analyses using polygenic regression models, liability threshold models, and bivariate trait analyses implemented in the SOLAR software were conducted after accounting for obesity, insulin resistance, and relative abundance of various lipoprotein fractions. Diacylglycerols, in general, and the DG 16:0/22:5 and DG 16:0/22:6 lipid species, in particular, were significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), as well as liability of incident hypertension measured during 7140.17 person-years of follow-up. Four lipid species, including the DG 16:0/22:5 and DG 16:0/22:6 species, showed significant genetic correlations with the liability of hypertension in bivariate trait analyses. Our results demonstrate the value of plasma lipidomic profiling in the context of hypertension and identify disturbance of diacylglycerol metabolism as an independent biomarker of hypertension.
高血压既是代谢综合征的一个组成部分,也是一个独立的实体,其诊断、发病机制和治疗仍然是一个挑战。先前的研究已经证明了高血压与脂质代谢指标之间的联系。新型技术,如血浆脂质组学分析,有望更好地了解脂质代谢紊乱的疾病。然而,在墨西哥裔美国人等高危人群中,血浆脂质组学与高血压之间的关联尚未得到评估。利用正在进行的圣安东尼奥家庭心脏研究中的丰富数据和样本资源,我们通过将高效液相色谱与串联质谱相结合,对 42 个大型和扩展的墨西哥裔美国家庭中的 1192 个人进行了血浆脂质组学分析,共鉴定了 319 种脂质。在考虑肥胖、胰岛素抵抗和各种脂蛋白分数的相对丰度后,使用 SOLAR 软件中的多基因回归模型、 LIABILITY 阈值模型和双变量特征分析进行了稳健的统计分析。总的来说,二酰基甘油(DG),特别是 DG 16:0/22:5 和 DG 16:0/22:6 脂质物种,与收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)显著相关,以及在 7140.17 人年的随访期间测量的高血压发病 LIABILITY。在双变量特征分析中,包括 DG 16:0/22:5 和 DG 16:0/22:6 在内的 4 种脂质物种与高血压发病 LIABILITY 具有显著的遗传相关性。我们的研究结果表明,血浆脂质组学分析在高血压方面具有价值,并确定二酰基甘油代谢紊乱是高血压的一个独立生物标志物。