Identification of the promoter of human carbonyl reductase 3 (CBR3) and impact of common promoter polymorphisms on hepatic CBR3 mRNA expression.
Identification of the promoter of human carbonyl reductase 3 (CBR3) and impact of common promoter polymorphisms on hepatic CBR3 mRNA expression.
复制标题
人羰基还原酶 3 (CBR3) 启动子的鉴定及常见启动子多态性对肝 CBR3 mRNA 表达的影响。
DOI：
10.1007/s11095-009-9936-9
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发表时间：
2009
影响因子：
3.7
通讯作者：
Blanco,JavierG
中科院分区：
文献类型：
--
作者：
Zhang,Jianping;Blanco,JavierG
目的近年来的研究表明，人羰基还原酶3（CBR 3）基因多态性影响阿霉素的药效学。首先，我们试图确定CBR 3的启动子。接下来，我们研究了两个CBR 3启动子多态性（CBR 3 - 725 T>C和CBR 3 - 326 T>A）是否决定启动子活性和hepaticCBR 3 mRNA levels.MethodsThe启动子活性的CBR 3报告结构进行了研究，在HepG 2和MCF-7细胞。CBR 3 mRNA水平记录在95个肝脏样本从白色（n= 62）和黑色（n= 33）供体。基因型-表型相关分析用于确定theCBR 3 - 725 T>C和CBR 3 - 326 T>A多态性对肝细胞CBR 3 mRNA水平的影响。来自黑人供体的肝脏样品显示出比来自白人的样品更高的相对CBR 3 mRNA水平（CBR 3 mRNA黑人= 3.0 ± 3.1相对倍数，CBR 3 mRNA白人= 1.6 ± 1.5相对倍数，p= 0.021）。变异的-725C和-326A等位基因没有改变工程化CBR 3启动子构建体的基因报告活性。在线，hepaticCBR 3 mRNA水平与CBR 3 - 725 T>C和CBR 3 - 326 T>A基因型status.ConclusionsThese研究提供了第一个洞察到的调节和可变的肝脏表达polymoricCBR 3。
PurposeRecent studies suggest that polymorphisms in human carbonyl reductase 3 (CBR3) influence the pharmacodynamics of doxorubicin. First, we sought to identify the promoter ofCBR3. Next, we examined whether twoCBR3promoter polymorphisms (CBR3-725T>C andCBR3-326T>A) dictate promoter activity and hepaticCBR3mRNA levels.MethodsThe promoter activities ofCBR3reporter constructs were investigated in HepG2 and MCF-7 cells.CBR3mRNA levels were documented in 95 liver samples from white (n= 62) and black (n= 33) donors. Genotype-phenotype correlation analyses were used to determine the impact of theCBR3-725T>C andCBR3-326T>A polymorphisms on hepaticCBR3mRNA levels.ResultsWe identified the promoter of humanCBR3. Liver samples from black donors showed higher relativeCBR3mRNA levels than samples from whites (CBR3mRNAblacks= 3.0 ± 3.1 relative foldvs.CBR3mRNAwhites= 1.6 ± 1.5 relative fold,p= 0.021). The variant -725C and -326A alleles did not modify the gene reporter activities of engineeredCBR3promoter constructs. In line, hepaticCBR3mRNA levels were not associated withCBR3-725T>C andCBR3-326T>A genotype status.ConclusionsThese studies provide the first insights into the regulation and variable hepatic expression of polymorphicCBR3.