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Human 3beta-hydroxysteroid dehydrogenase types 1 and 2: Gene sequence variation and functional genomics
Liewei Wang1, Ezequiel Salavaggione, Linda Pelleymounter
1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. wang.liewei@mayo.edu
The Journal of Steroid Biochemistry and Molecular Biology
|August 11, 2007
Summary
Genetic variations in HSD3B1 and HSD3B2 genes, crucial for steroid hormone synthesis, were identified. Some variations impact enzyme quantity, providing a basis for studying their role in hormone-related diseases.
Area of Science:
- Genetics
- Biochemistry
- Molecular Biology
Background:
- 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (HSD3B1 and HSD3B2) are key enzymes in steroid hormone biosynthesis.
- Genetic variations in these enzymes may contribute to steroid hormone-related diseases.
Purpose of the Study:
- To systematically identify common polymorphisms and haplotypes in human HSD3B1 and HSD3B2 genes.
- To investigate the functional impact of identified genetic variations on enzyme expression and localization.
Main Methods:
- Resequencing of HSD3B1 and HSD3B2 in 240 DNA samples from diverse ethnic groups.
- Functional genomic studies including expression analysis and immunofluorescence microscopy.
- Analysis of 5'-flanking region haplotypes for transcriptional activity.
Main Results:
- Identified 17 single nucleotide polymorphisms (SNPs) in HSD3B1 and 9 in HSD3B2, many novel.
- Two non-synonymous SNPs in HSD3B1 significantly reduced enzyme protein quantity.
- No significant alteration in subcellular localization for SNPs in membrane-binding domains.
- Common haplotypes in 5'-flanking regions showed cell line-dependent variations in transcriptional activity.
Conclusions:
- Common genetic variations in HSD3B1 and HSD3B2 genes have been identified.
- Specific polymorphisms affect enzyme protein levels, suggesting a role in disease pathophysiology.
- Transcriptional regulation by 5'-flanking haplotypes varies, contributing to genetic impact.
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