The lipoprotein lipase (Asn291->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia
The lipoprotein lipase (Asn291->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia
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DOI：
10.1016/0021-9150(95)05641-6
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发表时间：
1996-01-26
期刊：
影响因子：
5.3
通讯作者：
Frants, RR
中科院分区：
文献类型：
--
作者：
Hoffer, MJV;Bredie, SJH;Frants, RR
家族性混合性高脂血症(FCHL)是冠心病(CHD)的主要遗传原因之一，其特征是单个家庭内个体的血浆胆固醇和/或甘油三酯水平升高。脂蛋白脂酶(LPL)活性降低在某些FCHL病例中被发现。最近的一项研究揭示了一种常见的LPL基因突变，LPL(Asn291-->；Ser)，在荷兰FCHL患者中的频率为9.3%(Remer等人，循环，90(1994)I-998)。17个FCHL家系中有3个发现该突变。随后进行了广泛的家系研究，以确定该突变对FCHL表型表达的影响。使用基于系谱的最大似然估计，我们证明了LPL(Asn291-->；Ser)突变显著影响血浆和极低密度脂蛋白甘油三酯水平(携带者和非携带者分别为2.03+/-0.21比1.14+/-0.13和1.21+/-0.16比0.62+/-0.09 mmol/L)以及极低密度脂蛋白和高密度脂蛋白胆固醇水平(0.83+/-0.10比0.38+/-0.06和1.02+/-0.08比1.29+/-0.05 mmol/L)，携带者和非携带者)，但不是血浆和低密度脂蛋白(LDL)胆固醇的携带者。这些发现表明，LPL(Asn291-->；Ser)突变与血脂水平升高有关，这表明它可能是在所研究的家族中易患FCHL的遗传因素之一。
Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common mutation in the LPL gene, LPL(Asn291 --> Ser), with a frequency of 9.3% in Dutch FCHL patients (Reymer et al., Circulation, 90 (1994) I-998). This mutation was found in 3 out of 17 FCHL families. Extensive family studies were subsequently performed to determine the effect of this mutation on the phenotypic expression of FCHL. Using a pedigree-based maximum likelihood estimate, we demonstrated that the LPL(Asn291 --> Ser) mutation significantly affects the levels of plasma and very low density lipoprotein (VLDL) triglycerides (2.03 +/- 0.21 vs. 1.14 +/- 0.13 and 1.21 +/- 0.16 vs. 0.62 +/- 0.09 mmol/l, carriers and non-carriers, respectively) and VLDL- and high density lipoprotein (HDL) cholesterol (0.83 +/- 0.10 vs. 0.38 +/- 0.06 and 1.02 +/- 0.08 vs. 1.29 +/- 0.05 mmol/l, carriers and non-carriers, respectively), but not those of plasma and low density lipoprotein (LDL) cholesterol. These findings indicate that the LPL(Asn291 --> Ser) mutation is associated with elevated lipid levels, indicating it may be one of the genetic factors predisposing to FCHL in the families studied.