Berge Knut E, von Bergmann Klaus, Lutjohann Dieter, Guerra Rudy, Grundy Scott M, Hobbs Helen H, Cohen Jonathan C
The Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390-9052, USA.
J Lipid Res. 2002 Mar;43(3):486-94.
The plasma concentrations of cholesterol precursor sterols and plant sterols vary over a 5- to 10-fold range among normolipidemic individuals, and provide indices of the relative rates of cholesterol synthesis and fractional absorption. In the present study, we examined the relative contributions of genetic and environmental factors to variation in the plasma concentrations and sterol-cholesterol ratios of five noncholesterol sterols, including the 5alpha-saturated derivative of cholesterol (cholestanol), two precursors in the cholesterol biosynthesis pathway (desmosterol and lathosterol), and two phytosterols (campesterol and sitosterol). Plasma sterol concentrations were highly stable in 30 individuals measured over a 48 week period. Regression of offspring sterol levels on the parental values indicated that plasma levels of all five noncholesterol sterols were highly heritable. Analysis of monozygotic and dizygotic twin pairs also indicated strong heritability of all five sterols. Two common sequence variations (D19H and T400K) in ABCG8, an ABC half-transporter defective in sitosterolemia, were associated with lower concentrations of plant sterols in parents, and in their offspring.Taken together, these findings indicate that variation in the plasma concentrations of noncholesterol sterols is highly heritable, and that polymorphism in ABCG8 contributes to genetic variation in the plasma concentrations of plant sterols.
在血脂正常的个体中，胆固醇前体甾醇和植物甾醇的血浆浓度在5至10倍的范围内变化，并提供胆固醇合成相对速率和分数吸收的指标。在本研究中，我们研究了遗传和环境因素对五种非胆固醇甾醇血浆浓度和甾醇 - 胆固醇比率变化的相对贡献，这五种非胆固醇甾醇包括胆固醇的5α - 饱和衍生物（胆甾烷醇）、胆固醇生物合成途径中的两种前体（羊毛甾醇和谷甾醇）以及两种植物甾醇（菜油甾醇和甾醇）。在48周期间对30名个体进行测量，血浆甾醇浓度高度稳定。后代甾醇水平对亲本值的回归表明，所有五种非胆固醇甾醇的血浆水平都具有高度遗传性。对同卵双胞胎和异卵双胞胎的分析也表明所有五种甾醇都具有很强的遗传性。ABCG8（一种在谷甾醇血症中存在缺陷的ABC半转运蛋白）中的两个常见序列变异（D19H和T400K）与父母及其后代中较低的植物甾醇浓度相关。综上所述，这些发现表明非胆固醇甾醇血浆浓度的变化具有高度遗传性，并且ABCG8中的多态性导致植物甾醇血浆浓度的遗传变异。
