GENETIC DETERMINANT OF PHENOTYPIC VARIANCE OF MOLECULAR-WEIGHT OF LOW-DENSITY LIPOPROTEIN
GENETIC DETERMINANT OF PHENOTYPIC VARIANCE OF MOLECULAR-WEIGHT OF LOW-DENSITY LIPOPROTEIN
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DOI：
10.1073/pnas.72.6.2347
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发表时间：
1975-01-01
影响因子：
11.1
通讯作者：
WARMKE, GL
中科院分区：
文献类型：
--
作者：
FISHER, WR;HAMMOND, MG;WARMKE, GL
单分散人血浆低密度脂蛋白的分子量在2.4至3.9×10~(-6)的范围内变化。相比之下，对特定个体的两次不同场合测量的低密度脂蛋白的平均分子量差异为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认为是不同的大分子。低密度脂蛋白的分子量分布不受年龄和性别的影响。具有单分散低密度脂蛋白的高脂血症患者的分子量分布与正常受试者相似，早发冠状动脉疾病患者也是如此。家系研究表明，亲代与子代的平均分子质量之间的相关系数为0.82，相关系数为0.01。为评价环境对低密度脂蛋白相对分子质量的影响，测定了父亲和母亲低密度脂蛋白之间的相关系数，无统计学意义。这些数据被解释为低密度脂蛋白分子量遗传决定的有力证据。对五个家系的个体进行的研究发现，分子量数据符合无显性遗传模式的单基因座遗传模式。亲本低密度脂蛋白平均相对分子质量对后代相对分子质量的回归系数为0.30。如果分子量的变异性被认为是表型变异的一种表达，那么回归分析发现这种表型变异的30%可能是由加性基因作用引起的，推测是在单个基因座上。家庭数据中的种族隔离是一致的。由于低密度脂蛋白分子量的差异是由于与载脂蛋白结合的脂类的量不同引起的，因此分子量表型差异的另一部分可能是低密度脂蛋白代谢的个体差异造成的，从而产生脂含量的差异。低密度脂蛋白分子量的个体差异仅为5%左右，因此必须对影响低密度脂蛋白分子量的代谢序列进行精确控制。
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.