Functional characterization of seven single-nucleotide polymorphisms of the steroid sulfatase gene found in a Japanese population

Steroid Sulfatase (STS) is an Enzyme that hydrolyzes steroid sulfates such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate. STS has a key role in the synthesis of steroid Hormones in placenta and breast Cancer cells. Recently, we have identified six novel single-nucleotide polymorphisms (SNPs) and one nonsynonymous SNP (V476M) in the STS gene in a Japanese population. To clarify the effects of SNPs in the 5'-flanking region or 5' untranslated region on transcriptional activity, a reporter gene assay was conducted. In addition, DHEA-S desulfatase activity of a variant (Met at codon 476)-type Enzyme was compared with that of the wild (Wd)-type Enzyme in COS-1 cells. The transcriptional activities were significantly decreased (155A) and increased (-2837A and -1588C) in MCF-7 cells. On the Other hand, no significant difference was found in expression levels of STS protein or specific activities of DHEA-S desulfation between Wd and the variant Enzymes. This is the first report on the effects of various SNPs in the STS gene detected in Japanese healthy subjects.