Kastelein J J, Ordovas J M, Wittekoek M E, Pimstone S N, Wilson W F, Gagné S E, Larson M G, Schaefer E J, Boer J M, Gerdes C, Hayden M R
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Clin Genet. 1999 Oct;56(4):297-305. doi: 10.1034/j.1399-0004.1999.560407.x.
We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (delta = - 0.07 mmol/ 1, p = 0.03) and a trend towards increased triglycerides (delta = 0.25 mmol/ 1, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (delta = - 0.02 mmol/1 for HDL-C and delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels for D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women.
我们评估了脂蛋白脂肪酶基因（LPL）中的两种常见突变D9N和N291S的作用，这两种突变已被证明可在广泛的患者群体中调节血脂。对来自弗雷明汉后代研究（FOS）的1114名男性和1144名女性进行了这两种LPL变异的分析。随后，确定了其与空腹血脂及冠状动脉疾病（CHD）风险的关联。我们通过计算遗传性血脂异常患者、CHD患者和健康对照中这些LPL突变携带者和非携带者的血脂及脂蛋白加权平均值来扩展我们的研究。在FOS样本中，D9N和N291S等位基因与较低的高密度脂蛋白胆固醇（HDL-C）相关（差异=-0.07 mmol/1，p=0.03），且有甘油三酯升高的趋势（差异=0.25 mmol/1，p=0.07）。在女性中，高甘油三酯、低HDL-C表型的趋势明显（HDL-C差异=-0.02 mmol/1，甘油三酯差异=0.14 mmol/l）。对D9N和N291S男性携带者的其他研究进行累积分析发现，甘油三酯水平较高（D291N；2.60(1.85) mmol/l对1.62(1.18) mmol/l：p<0.0001）（D9N；1.94(1.19) mmol/l对1.74(1.17) mmol/l：p<0.001），HDL-C较低（N291S；1.04(0.32) mmol/l对1.15(0.28) mmol/l：p<0.0001）（D9N；1.08(0.24) mmol/l对1.16(0.28) mmol/l：p<0.000）。在女性中，结果有所不同，甘油三酯水平较高（N291S；1.70(0.99) mmol/l对1.10(0.63) mmol/l：p<0.001）（D9N；1.08(0.76) mmol/l对0.96(0.51) mmol/l：p<0.01），HDL-C水平较低（N291S；1.27(0.33) mmol/l对1.51(0.32) mmol/l：p<0.0001）；然而，D9N携带者的HDL-C水平与非携带者相似（D9N；1.52(0.29) mmol/l对1.53(0.35) mmol/l：p=0.83）。我们的数据提供了证据，表明LPL基因的常见变异是男性和女性血脂及脂蛋白水平重要的调节因素。
