Human 3β-hydroxysteroid dehydrogenase types 1 and 2: Gene sequence variation and functional genomics

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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
Issue number1-2
StatePublished - Oct 2007


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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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