Single nucleotide polymorphisms of 17beta-hydroxysteroid dehydrogenase type 7 gene: mechanism of estramustine-related adverse reactions?
OBJECTIVE
To investigate the influence of single nucleotide polymorphisms (SNP) on transcription of the 17beta-hydroxysteroid dehydrogenase (HSD17B7) gene.


METHODS
Luciferase reporter genes containing a 5'-flanking of the HSD17B7 gene, as well as the sequence around the SNP, were transfected into LNCaP and DU145 cells. Then, luciferase assays were carried out.


RESULTS
The presence of the G allele resulted in an increase of transcriptional activity derived from the 5'-flanking region of the HSD17B7 gene by 270% and 370% in LNCaP and DU145 cells, respectively. Transcriptional activity of the HSD17B7 gene containing the G allele was higher than that of the C allele.


CONCLUSIONS
The transcriptional activity of the HSD17B7 gene containing the G allele is higher than that of the C allele. This difference in HSD17B7 expression may regulate the risk of peripheral edema as an adverse reaction induced by estramustine phosphate sodium.
Ozeki
Takeshi
T
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Takeuchi
Megumi
M
Suzuki
Motofumi
M
Kitamura
Tadaichi
T
Takayanagi
Risa
R
Yokoyama
Haruko
H
Yamada
Yasuhiko
Y
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D004487:Edema / Q000139:chemically induced* / Q000235:genetics*; D004961:Estramustine / Q000009:adverse effects*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D004961:Estramustine; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase