Thyroid State Regulates Gene Expression in Human Whole Blood

Abstract

Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRα-expressing leukocytes. In addition, TH may regulate gene transcripts in platelets.

Empowering thyroid hormone research in human subjects using OMICs technologies

“…A TH-dependent suppression of the degradation of asymmetric dimethyl arginine was already named. Furthermore, the increased amount of transcripts specific for platelets following L-T 4 treatment (Massolt et al 2017) might indicate an activated state and hence activation of the coagulation cascade, which well aligns with numerous observational studies. A more complex example might be given by use of kynurenine as key metabolite (Fig.…”

“…tissue-depending gene expression pattern following TH treatment using array-based techniques in muscle biopsies (Clement et al 2002, Visser et al 2009), adipocyte explants (Viguerie et al 2002) or fibroblasts (Moeller et al 2005), and more recently, whole blood samples from athyroid patients analyzed by next-generation sequencing (Massolt et al 2017) (Table 1). Clement et al (2002) were the first to analyze gene expression in skeletal muscles from healthy human males treated with T 3 for 14 days.…”

“…They mostly exert negative regulation and indeed a significant overlap between predicted miR-133b targets and downregulated DEGs was found. In a later study (Massolt et al 2017), the authors investigated whole blood gene expression. Although they found only little overlap with their previous work (attributed to the specific role of TH in hemostasis), they identified a novel cluster of snoRNAs that were downregulated in response to THs.…”

“…Tissue-specific gene expression patterns following TH treatment were further observed in human adipocyte explants (Viguerie et al 2002), cultured fibroblast (Moeller et al 2005) and circulating whole blood (Massolt et al 2017). Briefly, T 3 treamtent of human adipocyte explants changed the expression of 19 genes (13 upregulated and 6 downregulated) (Viguerie et al 2002).…”

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy

“…Therefore, we used patients with DTC as a model to quantify serum levels of 384 miRNAs in different thyroid states. Since we were previously able to detect significant changes in numerous gene transcripts in peripheral blood as well as in muscle samples in respectively 8 and 10 patients, while using a similar study design, we postulated that 13 patients would be enough to identify clinically relevant markers [ 13 , 17 ]. Using alpha = 0.05 and power = 80%, we would be able to detect a Cohen’s d effect size of 0.87, which is considered as a large effect.…”