Common polymorphisms in the CYP7A1 gene do not contribute to variation in rates of bile acid synthesis and plasma LDL cholesterol concentration
Common polymorphisms in the CYP7A1 gene do not contribute to variation in rates of bile acid synthesis and plasma LDL cholesterol concentration
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DOI：
10.1016/j.atherosclerosis.2005.01.032
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发表时间：
2005-09-01
期刊：
影响因子：
5.3
通讯作者：
van't Hooft, FM
中科院分区：
文献类型：
--
作者：
Abrahamsson, A;Krapivner, S;van't Hooft, FM
胆固醇7 α-羟化酶（CYP 7AI）基因的转录调控对胆汁酸和胆固醇代谢至关重要。我们评估了CYP 7AI基因启动子区两种常见多态性（-203 C/A和-469 T/C）的生理意义。在使用天然834 bp启动子构建体的瞬时转染研究中，没有发现-203 C和-203 A等位基因或-469 T和-469 C等位基因之间存在生理差异的证据。此外，在胆石病受试者中分析，CYP 7AI启动子多态性与肝胆固醇7 α-羟化酶活性和胆汁酸合成速率参数之间未观察到相关性。此外，在三组不同的瑞典中年男性中进行的相关研究中，未发现启动子多态性与血浆LDL胆固醇浓度之间的关系。最后，两个启动子多态性与CYP 7A 1基因3'端的IVS 6 + 363 G/A多态性之间存在几乎完全的等位基因关联（竖线D'竖线= 0.98），表明整个CYP 7A 1基因存在很强的连锁不平衡。它的结论是，共同的CYP 7AI基因多态性不有助于胆固醇7 α-羟化酶活性的变化，胆汁酸合成率和血浆LDL胆固醇浓度在人类。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Transcriptional regulation of the cholesterol 7 alpha-hydroxylase (CYP7AI) gene is of critical importance for bile acid and cholesterol metabolism. We evaluated the physiological significance of two common polymorphisms (-203C/A and -469T/C) in the promoter region of the CYP7AI gene, No evidence was found for physiological differences between either the -203C and -203A alleles or the -469T and -469C alleles in transient transfection studies using native 834 bp promoter constructs. Moreover, no association was observed between the CYP7AI promoter polymorphisms and the hepatic cholesterol 7 alpha-hydroxylase activity and parameters of bile acid synthesis rates, as analyzed in subjects with gallstone disease. In addition, no relationships were found between the promoter polymorphisms and plasma LDL cholesterol concentration in association studies conducted in three different groups of middle-aged Swedish men. Finally, near complete allefic association was found between the two promoter polymorphisms and the IVS6 + 363G/A polymorphism at the 3' end of the CYP7AI gene (vertical bar D'vertical bar = 0.98), indicating strong linkage disequilibrium across the whole CYP7AI gene. It is concluded that common polymorphisms of the CYP7AI gene do not contribute to variation in cholesterol 7 alpha-hydroxylase activity, rates of bile acid synthesis and plasma LDL cholesterol concentration in humans. (c) 2005 Elsevier Ireland Ltd. All rights reserved.