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

Abstract

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>In men, positive correlations were detected between AD and <i>DDIT4 </i>mRNA levels, as well as between SHBG and the mRNA levels of <i>RPIA</i>, <i>RIOK3</i>, <i>GYPB</i>, <i>BPGM</i>, and <i>RAB2B</i>. No additional significant associations were observed.</p><p>Conclusions</p><p>Besides the associations between AD and <i>DDIT4</i> expression and SHBG and the transcript levels of <i>RPIA</i>, <i>RIOK3</i>, <i>GYPB</i>, <i>BPGM</i>, and <i>RAB2B</i>, 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.</p></div