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A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio.

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.

SUBMITTER: Haring R

PROVIDER: S-EPMC3535724 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio.

Haring Robin R Wallaschofski Henri H Teumer Alexander A Kroemer Heyo H Taylor Angela E AE Shackleton Cedric H L CH Nauck Matthias M Völker Uwe U Homuth Georg G Arlt Wiebke W

Journal of molecular endocrinology 20121231 1

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 ...[more]

PMID: 23132913

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Project description:BackgroundExisting literature suggests that endocrine measures, including the steroid hormones of cortisol and Dehydroepiandrosterone (DHEA), as well as the DHEA to cortisol ratio in the human hair can be used as promising biomarkers of chronic stress among humans. However, data are limited regarding the validity of these measures as biomarkers of chronic stress among people living with HIV (PLWH), whose endocrine system or hypothalamic pituitary adrenal (HPA) axis may be affected by HIV infection and/or antiretroviral therapy (ART) medications.MethodUsing hair sample data and self-reported survey from 60 PLWH in China, we examined the validity of three endocrine measures among Chinese PLWH using a known-groups validation strategy. High-stress group (n = 30) and low-stress group (n = 30) of PLWH were recruited through individual assessment interviews by a local licensed psychologist. The endocrine measures in hair were extracted and assessed by LC-APCI-MS/MS method. Both bivariate and multivariate analyses were conducted to examine the associations between the endocrine measures and the stress level, and to investigate if the associations differ by ART status.ResultsThe levels of endocrine measures among Chinese PLWH were consistent with existing studies among PLWH. Generally, this pilot study confirmed the association between endocrine measures and chronic stress. The high stress group showed higher level hair cortisol and lower DHEA to cortisol ratio. The higher stress group also reported higher scores of stressful life events, perceived stress, anxiety and depression. Hair cortisol level was positively related to anxiety; DHEA was negatively associated with stressful life events; and the DHEA to cortisol ratio was positively related to stressful life events and perceived stress. ART did not affect the associations between the endocrine measures and stress level.ConclusionsOur findings suggest that hair cortisol and DHEA to cortisol ratio can be used as promising biomarkers of chronic stress among PLWH. Clarifying the role of steroid hormones in the psychoimmunology of PLWH may yield important implications for clinical practice and psychological intervention.

Dataset Information

A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio.

Publications

A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS does not impact on the actual DHEA/DHEAS ratio.

Similar Datasets

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