Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.
Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.
复制标题
低密度脂蛋白受体基因的缺陷影响脂蛋白（a）水平：与过早动脉粥样硬化相关的两个基因位点的乘性相互作用。
DOI：
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发表时间：
1989
影响因子：
11.1
通讯作者：
Eric Boerwinkle
中科院分区：
文献类型：
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作者：
Gerd Utermann;F. Hoppichler;Hans Dieplinger;M. Seed;Gilbert R. Thompson;Eric Boerwinkle
脂蛋白(A)[Lp(A)]含有两种不同的蛋白质，载脂蛋白(Apo)B-100和一种特定的高分子量糖蛋白apo(A)。Lp(A)代表一种连续的数量遗传性状，其遗传学还知之甚少。载脂蛋白(A)基因座上的遗传变异影响血浆Lp(A)水平，并解释了这一性状至少40%的变异性。研究发现，具有一个突变低密度脂蛋白受体基因的杂合型家族性高胆固醇血症患者的血浆Lp(A)水平升高了3倍。这种升高不是由于家族性高胆固醇血症患者中那些与高Lp(A)水平相关的载脂蛋白(A)类型频率较高所致。相反，在所检测的每种载脂蛋白(A)表型中，Lp(A)水平均升高。载脂蛋白(A)和低密度脂蛋白受体基因对Lp(A)水平的影响不是相加的，而是乘性的。在数量人类遗传学中，这是一种通常不考虑的情况。我们认为，血浆Lp(A)水平可能是由多个基因位点的变异决定的。
The lipoprotein (a) [Lp(a)] contains two nonidentical protein species, apolipoprotein (apo) B-100 and a specific high molecular weight glycoprotein, apo(a). Lp(a) represents a continuous quantitative genetic trait, the genetics of which are only poorly understood. Genetic variation at the apo(a) locus affects plasma Lp(a) levels and explains at least 40% of the variability of this trait. Lp(a) levels were found to be elevated 3-fold in the plasma from patients with the heterozygous form of familial hypercholesterolemia who have one mutant low density lipoprotein receptor gene. This elevation was not due to a higher frequency of those apo(a) types that are associated with high Lp(a) levels in familial hypercholesterolemia patients. Rather Lp(a) levels were elevated for each of the apo(a) phenotypes examined. The effects of the apo(a) and low density lipoprotein receptor genes on Lp(a) levels are not additive but multiplicative. This is a situation not commonly considered in quantitative human genetics. We conclude that Lp(a) levels in plasma may be determined by variation at more than one gene locus.