TY - JOUR
T1 - A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio
AU - Haring, Robin
AU - Wallaschofski, Henri
AU - Teumer, Alexander
AU - Kroemer, Heyo K.
AU - Taylor, Angela E.
AU - Shackleton, Cedric H.L.
AU - Nauck, Matthias
AU - Völker, Uwe
AU - Homuth, Georg
AU - Arlt, Wiebke
PY - 2013
Y1 - 2013
N2 - 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 (nZ172) 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 inthe 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.
AB - 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 (nZ172) 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 inthe 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.
KW - DHEAS
KW - Epidemiology
KW - Genetics
KW - Genome-wide association study
KW - Steroids
UR - http://www.scopus.com/inward/record.url?scp=84872041810&partnerID=8YFLogxK
U2 - 10.1530/JME-12-0185
DO - 10.1530/JME-12-0185
M3 - Article
C2 - 23132913
AN - SCOPUS:84872041810
SN - 0952-5041
VL - 50
SP - 73
EP - 77
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
IS - 1
ER -
