The A-204C Polymorphism in CYP7A1 Gene Affects Its Promoter Activity / 中国生物化学与分子生物学报

ABSTRACT

cholesterol 7α-hydroxylase gene ( CYP7A 1 ) plays a key role in the catabolism of cholesterol into bile acids. To investigate whether the A-204C polymorphism in CYP7A1 gene affects the gene expression,using luciferase as the reporter gene, four recombinants were constructed by inserting forward or reverse sequence with A or C allele at the polymorphism site into the promoter-less vector pGL3-basic. The constructs were then transfected into four cell lines and the luciferase activity of each expression vector was examined by dual luciferase reporter gene assay system. The results showed that activities of the forward sequence of both genotypes were higher than that of reverse sequence. Promoter activity of the recombinants with A allele was about one third lower than that with C allele. According to the analysis with TRANSFAC database, there may exist a Zic3 binding site when there is the C allele at -204. Our study indicates that the A-204 C polymorphism in CYP7A1 promoter region decreases its promoter activity and thus represses the gene expression, possibly due to the lack of a potential Zic3 binding site.