Linkage between cholesterol 7α-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations
Linkage between cholesterol 7α-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations
复制标题
DOI：
10.1172/jci1343
复制
发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Cohen, JC
中科院分区：
文献类型：
--
作者：
Wang, JP;Freeman, DJ;Cohen, JC
血浆低密度脂蛋白胆固醇（LDL-C）水平的个体间差异反映了环境变异和遗传多态性，但具体涉及的基因及其对LDL-C差异的相对贡献尚不清楚。在这项研究中，我们研究了血浆LDL- c浓度与三个在LDL代谢中起关键作用的基因之间的关系：低密度脂蛋白受体（LDLR）、载脂蛋白B （APOB）和胆固醇7 α -羟化酶（CYP7）。对150个核心家族的分析表明，血浆LDL- c浓度与CYP7有统计学意义的联系，但LDLR或APOB没有统计学意义。进一步的兄弟姐妹对分析使用高血浆LDL-C浓度作为先证者的个体表明CYP7位点与高血浆LDL-C有关，但与低血浆LDL-C浓度无关。这一发现在一个独立的样本中得到了重复。DNA测序显示CYP7的5'侧区有两个连锁多态性。这些多态性定义的等位基因与血浆LDL-C浓度升高有关，无论是在兄弟姐妹中还是在无血缘关系的个体中。综上所述，这些发现表明CYP7的多态性有助于血浆LDL-C浓度的遗传变异。在普通人群中，LDLR和APOB的常见多态性只占血浆LDL-C浓度遗传变异的很小一部分。
Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7 alpha-hydroxylase (CYP7), Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population.