Associations between Serum Sex Hormone Concentrations and Whole Blood Gene Expression Profiles in the General Population

PLoS One. 2015 May 22;10(5):e0127466. doi: 10.1371/journal.pone.0127466. eCollection 2015.

Abstract

Background: Despite observational evidence from epidemiological and clinical studies associating sex hormones with various cardiometabolic risk factors or diseases, pathophysiological explanations are sparse to date. To reveal putative functional insights, we analyzed associations between sex hormone levels and whole blood gene expression profiles.

Methods: We used data of 991 individuals from the population-based Study of Health in Pomerania (SHIP-TREND) with whole blood gene expression levels determined by array-based transcriptional profiling and serum concentrations of total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (AD), estradiol (E2), and estrone (E1) measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay. Associations between sex hormone concentrations and gene expression profiles were analyzed using sex-specific regression models adjusted for age, body mass index, and technical covariables.

Results: In men, positive correlations were detected between AD and DDIT4 mRNA levels, as well as between SHBG and the mRNA levels of RPIA, RIOK3, GYPB, BPGM, and RAB2B. No additional significant associations were observed.

Conclusions: Besides the associations between AD and DDIT4 expression and SHBG and the transcript levels of RPIA, RIOK3, GYPB, BPGM, and RAB2B, the present study did not indicate any association between sex hormone concentrations and whole blood gene expression profiles in men and women from the general population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Androstenedione / blood*
  • Body Mass Index
  • Dehydroepiandrosterone Sulfate / blood*
  • Estradiol / blood*
  • Estrone / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood*
  • Transcriptome*
  • Young Adult

Substances

  • Sex Hormone-Binding Globulin
  • Estrone
  • Testosterone
  • Androstenedione
  • Estradiol
  • Dehydroepiandrosterone Sulfate

Grants and funding

This work is part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg – West Pomerania (03IS2061A). Data collection was supported by the Community Medicine Research network (CMR) of the University of Greifswald, Germany, and is funded by the Federal Ministry of Education and Research, the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. The CMR encompasses several research projects that share data from the population-based Study of Health in Pomerania (SHIP; http://www.community-medicine.de). This study was also supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research, grant no. 03ZIK012). RH is the guarantor of this work, had full access to all the data, and takes full responsibility for the integrity of data and the accuracy of data analysis. Furthermore, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.