Identification of the promoter of human carbonyl reductase 3 (CBR3) and impact of common promoter polymorphisms on hepatic CBR3 mRNA expression.

ABSTRACT:

Purpose

Recent studies suggest that polymorphisms in human carbonyl reductase 3 (CBR3) influence the pharmacodynamics of doxorubicin. First, we sought to identify the promoter of CBR3. Next, we examined whether two CBR3 promoter polymorphisms (CBR3 -725T>C and CBR3 -326T>A) dictate promoter activity and hepatic CBR3 mRNA levels.

Methods

The promoter activities of CBR3 reporter constructs were investigated in HepG2 and MCF-7 cells. CBR3 mRNA 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 the CBR3 -725T>C and CBR3 -326T>A polymorphisms on hepatic CBR3 mRNA levels.

Results

We identified the promoter of human CBR3. Liver samples from black donors showed

SUBMITTER: Zhang J 

PROVIDER: S-EPMC3368600 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature