Human 3β-hydroxysteroid dehydrogenase types 1 and 2

Gene sequence variation and functional genomics

Liewei M Wang, Ezequiel Salavaggione, Linda Pelleymounter, Bruce Eckloff, Eric D Wieben, Richard M Weinshilboum

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The 3β-hydroxysteroid dehydrogenase/Δ54 isomerase isoenzymes 1 and 2 (HSD3B1 and HSD3B2) are membrane-bound enzymes that play essential roles in the biosynthesis of steroid hormones. Therefore, variation in the HSD3B1 and HSD3B2 genes might play a role in the pathophysiology of steroid hormone-related disease. We set out to systematically identify common polymorphisms and haplotypes in human HSD3B1 and HSD3B2. We identified 17 single nucleotide polymorphisms (SNPs) in HSD3B1 and 9 in HSD3B2 - the majority of which were not present in public databases - by resequencing human HSD3B1 and HSD3B2 using 240 DNA samples from four different ethnic groups (60 samples per group). Functional genomic studies of the five non-synonymous cSNPs in HSD3B1 and the one observed in HSD3B2 showed that two of these polymorphisms resulted in significant decreases in the quantity of enzyme protein expressed. However, none of the three non-synonymous SNPs located in areas encoding putative membrane-binding domains altered subcellular localization of the enzyme as determined by immunofluorescence microscopy. Finally, common variant haplotypes in the 5′-flanking regions of these genes showed significant cell line-dependent variation in their ability to drive transcription. In aggregate, these results provide a basis for study of the possible role in human disease of common genetic variation in HSD3B1 and HSD3B2.

Original languageEnglish (US)
Pages (from-to)88-99
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume107
Issue number1-2
DOIs
StatePublished - Oct 2007

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3-Hydroxysteroid Dehydrogenases
Genomics
Genes
Polymorphism
Steroid hormones
Haplotypes
Single Nucleotide Polymorphism
Enzymes
Nucleotides
Steroids
Hormones
Membranes
Isomerases
5' Flanking Region
Biosynthesis
Transcription
3 beta-hydroxysteroid dehydrogenase type II
Fluorescence Microscopy
Ethnic Groups
Isoenzymes

Keywords

  • 3β-Hydroxysteroid dehydrogenase 1
  • 3β-Hydroxysteroid dehydrogenase 2
  • Functional genomics
  • Gene resequencing
  • Genetic polymorphisms
  • Haplotypes
  • HSD3B1
  • HSD3B2
  • Single nucleotide polymorphisms
  • SNPs

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Human 3β-hydroxysteroid dehydrogenase types 1 and 2 : Gene sequence variation and functional genomics. / Wang, Liewei M; Salavaggione, Ezequiel; Pelleymounter, Linda; Eckloff, Bruce; Wieben, Eric D; Weinshilboum, Richard M.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 107, No. 1-2, 10.2007, p. 88-99.

Research output: Contribution to journalArticle

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