Reymer P W, Gagné E, Groenemeyer B E, Zhang H, Forsyth I, Jansen H, Seidell J C, Kromhout D, Lie K E, Kastelein J
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Nat Genet. 1995 May;10(1):28-34. doi: 10.1038/ng0595-28.
A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with significantly reduced HDL levels (P = 0.001) and results in a significant decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this mutation increases in those patients with lower HDL cholesterol levels. In vitro mutagenesis and expression studies confirm that this change is associated with a significant reduction in LPL activity. Our data support the relationship between LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a factor in the development of atherosclerosis.
高密度脂蛋白胆固醇（HDL-C）降低被认为是冠状动脉疾病（CAD）的一个重要危险因素。我们现在发现，在大约二十分之一经证实患有动脉粥样硬化的男性中，人类脂蛋白脂肪酶（LPL）基因中的Asn291Ser突变与HDL水平显著降低相关（P = 0.001），并导致LPL催化活性显著下降（P < 0.0009）。在HDL胆固醇水平较低的患者中，这种突变的相对频率增加。体外诱变和表达研究证实，这种变化与LPL活性显著降低有关。我们的数据支持LPL活性与HDL-C水平之间的关系，并表明特定的LPL突变可能是动脉粥样硬化发展的一个因素。
