A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia.
A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia.
复制标题
脂蛋白脂肪酶基因 (Asn291Ser) 中频繁发生的突变导致家族性混合性高脂血症的表达。
DOI：
10.1093/hmg/4.9.1543
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发表时间：
1995
影响因子：
3.5
通讯作者：
John J. P.Kastelein
中科院分区：
文献类型：
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作者：
P. Reymer;B. E. Groenemeyer;Eric Gagné;Li Miao;Elianne E.G. Appelman;Jaap C. Seidel;D. Kromhout;S. M. Bijvoet;Karin van de Oever;Taco Bruin;Michael R. Hayden;John J. P.Kastelein
对169例无血缘关系的男性家族性混合性高脂血症患者进行了LPL基因第4、5、6外显子及其外显子-内含子边界的变性梯度凝胶电泳法分析。对20例患者进行了外显子6的核苷酸替换。测序和聚合酶链式反应分析均发现一种常见的突变(Asn291Ser)。该突变在215名男性对照组中也存在，但频率低于FCH患者(10/215=4.6%vs.20/169=11.8%；p<；0.02)。对血脂、脂蛋白和载脂蛋白水平的分析表明，在我们的对照组中，Asn291Ser突变的存在与高密度脂蛋白-胆固醇降低(0.94+/-0.31vs.1.12+/-0.26 mmol/L；p<；0.04)相关。与非携带者相比，携带该突变的FCH患者高密度脂蛋白-胆固醇水平降低(0.75+/-0.16vs.0.95+/-0.36mmoL/L；p=0.005)，甘油三酯水平升高(5.96+/-4.12vs.3.48+/-1.78mmol/L；p<；0.005)。当BMI超过27 kg/m2时，这种替代的携带者的高甘油三酯和低高密度脂蛋白的表型最为明显。我们对男性FCH患者的研究发现，LPL-基因存在一个与脂蛋白异常相关的常见突变，表明LPL缺陷至少是导致FCH-表型的因素之一。
We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.