Fisher W R, Hammond M G, Mengel M C, Warmke G L
Proc Natl Acad Sci U S A. 1975 Jun;72(6):2347-51. doi: 10.1073/pnas.72.6.2347.
The molecular weight of monodisperse human plasma low densitylipoprotein has been measured in 69 individuals and found to vary over the range of 2.4 to 3.9 X 10-6. By contrast, the molecular weight of low density lipoprotein measured on two separate occasions for specific individuals shows a mean difference of 0.07 X 10-6 and a standard deviation of 0.08 X 10-6; hence low density lipoprotein differing in molecular weight by greater than 0.2 X 10-6 may be considered different macomolecules. The distribution of the molecular weight of low density lipoprotein does not differ as a function of age or sex. Hyperlipemic subjects having monodisperse low density lipoprotein show similar molecular weight distribution to normal subjects, as do subjects with premature coronary artery disease. Family studies reveal a correlation coefficient of 0.82 between average molecular weights of parents and offspring, with significance at 0.01. In order to assess the influence of environment on molecular weight of low density lipoprotein, the correlation coefficient between the fathers' and mothers' low density lipoprotein was measured and no statistically significant correlation was found. These data are interpreted as strong evidence for a genetic determination of molecular weight of low density lipoprotein. A study of individuals in five families yields molecular weight data consistent with a single gene locus genetic mode of inheritance without dominance. The regression coefficient of the mean low denisty lipoprotein parental molecular weight on the offspring molecular weight is 0.30. If the variability of molecular weight is considered as an expression of phenotypic variance, then the regression analysis identified 30% of this phenotypic variance as arising from additive gene action presumably at a single locus. Segregation in the family data is consistent. Since the differences in molecular weight of low density lipoprotein arise from differences in the amount of lipid bound to the apoprotein, it is likely that an additional portion of the phenotypic variance of the molecular weight results from individual variations in the metabolism of low density lipoprotein, which yield differences in lipid content. The individual variation in molecular weight is only approximately 5%; hence those metabolic sequences that influence molecular weight of low density lipoproteins must be precisely controlled.
已对69名个体的单分散人血浆低密度脂蛋白的分子量进行了测量，发现其在2.4至3.9×10⁻⁶的范围内变化。相比之下，对特定个体在两个不同时间测量的低密度脂蛋白分子量，平均差异为0.07×10⁻⁶，标准差为0.08×10⁻⁶；因此，分子量差异大于0.2×10⁻⁶的低密度脂蛋白可被视为不同的大分子。低密度脂蛋白分子量的分布不因年龄或性别而异。患有单分散低密度脂蛋白的高脂血症患者与正常受试者的分子量分布相似，患有早发性冠状动脉疾病的受试者也是如此。家族研究显示，父母与后代的平均分子量之间的相关系数为0.82，在0.01水平上具有显著性。为了评估环境对低密度脂蛋白分子量的影响，测量了父亲和母亲的低密度脂蛋白之间的相关系数，未发现具有统计学意义的相关性。这些数据被解释为低密度脂蛋白分子量由遗传决定的有力证据。对五个家族中的个体进行的一项研究得出的分子量数据与无显性的单基因座遗传模式一致。后代分子量对亲代低密度脂蛋白平均分子量的回归系数为0.30。如果将分子量的变异性视为表型变异的一种表现，那么回归分析确定这种表型变异的30%可能是由单个基因座上的加性基因作用引起的。家族数据中的分离是一致的。由于低密度脂蛋白分子量的差异源于与载脂蛋白结合的脂质数量的差异，因此分子量表型变异的另一部分可能是由低密度脂蛋白代谢的个体差异导致脂质含量不同引起的。分子量的个体差异仅约为5%；因此，那些影响低密度脂蛋白分子量的代谢序列必须受到精确控制。
