A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
DHEA is the major precursor of human sex steroid synthesis and is inactivated via sulfonation to DHEAS. A previous genome-wide association study related the single nucleotide polymorphism (SNP) rs2637125, located near the coding region of DHEA sulfotransferase, SULT2A1, to serum DHEAS concentrations. However, the functional relevance of this SNP with regard to DHEA sulfonation is unknown. Using data from 3300 participants of the population-based cohort Study of Health in Pomerania, we identified 43 individuals being homozygote for the minor allele of the SNP rs2637125 (AA) and selected two sex- and age-matched individuals with AG and GG genotype (n=172) respectively. Steroid analysis including measurement of serum DHEA and DHEAS was carried out by liquid chromatography/mass spectrometry, employing steroid oxime analysis for enhancing the sensitivity of DHEA detection. We applied quantile regression models to compare median hormone levels across SULT2A1 genotypes. Median comparisons by SULT2A1 genotype (AA vs AG and GG genotypes respectively) showed no differences in the considered hormones including DHEAS, DHEA, androstenedione, as well as cortisol and cortisone concentrations. SULT2A1 genotype also had no effect on the DHEA/DHEAS ratio. Sex-stratified analyses, as well as alternative use of the SULT2A1 SNP rs182420, yielded similar negative results. Genetic variants of SULT2A1 do not appear to have an effect on individual DHEA and DHEAS concentrations or the DHEA/DHEAS ratio as a marker of DHEA sulfonation capacity.
Date Issued
2013-02-01
Date Acceptance
2012-11-06
Citation
Journal of Molecular Endocrinology, 2013, 50 (1), pp.73-77
ISSN
0952-5041
Publisher
BioScientifica
Start Page
73
End Page
77
Journal / Book Title
Journal of Molecular Endocrinology
Volume
50
Issue
1
Copyright Statement
© 2013 Society for Endocrinology Published by Bioscientifica Ltd. This is an Open Access article distributed under the terms of the Society for Endocrinology’s Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/23132913
PII: JME-12-0185
Subjects
CELLS
DEHYDROEPIANDROSTERONE-SULFATE
DHEAS
Endocrinology & Metabolism
epidemiology
genetics
genome-wide association study
Life Sciences & Biomedicine
Science & Technology
steroids
SULFONATION
SULFOTRANSFERASE SULT2A1
TRANSCRIPTION
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2013-02-01