Engler Mary B, Pullinger Clive R, Malloy Mary J, Natanzon Yanina, Kulkarni Medha V, Song James, Eng Celeste, Huuskonen Jaarko, Rivera Christopher, Poon Annie, Bensley Matt, Sehnert Amy, Zellner Christian, Kane John, Aouizerat Bradley E
Department of Physiological Nursing, University of California San Francisco, San Francisco, CA 94143, USA.
Metabolism. 2008 Dec;57(12):1719-24. doi: 10.1016/j.metabol.2008.07.031.
We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.
我们之前证明了磷脂转运蛋白（PLTP）基因变异（rs2294213）在低α脂蛋白血症（HypoA）中对高密度脂蛋白胆固醇（HDL-C）水平的影响。我们现在探讨了PLTP在高α脂蛋白血症（HyperA）中的作用。通过DNA熔解对107例高α脂蛋白血症患者的人类PLTP基因进行序列异常筛查，并评估其与血浆脂蛋白水平的相关性。我们检测到7个序列变异：1个先前报道的变异（rs2294213）和5个新突变，其中包括1个错义突变（L106F）。p.L106F突变的PLTP活性未发生改变。与对照组（4.3%）和低α脂蛋白血症组（2.2%）相比，rs2294213次要等位基因的频率在高α脂蛋白血症组中显著增加（7.0%）。此外，rs2294213与HDL-C水平密切相关。线性回归模型预测，rs2294213次要等位基因的存在可独立于甘油三酯升高HDL-C水平。这些发现将rs2294213与HDL-C水平的关联扩展到了HDL分布的极端情况。
