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- Title
Thyroid State Regulates Gene Expression in Human Whole Blood.
- Authors
Massolt, Elske T; Meima, Marcel E; Swagemakers, Sigrid M A; Leeuwenburgh, Selmar; van den Hout-van Vroonhoven, Mirjam C G M; Brigante, Giulia; Kam, Boen L R; van der Spek, Peter J; van IJcken, Wilfred F J; Visser, Theo J; Peeters, Robin P; Visser, W Edward
- Abstract
<bold>Context: </bold>Despite the well-recognized clinical features resulting from insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues.<bold>Objective: </bold>To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of T3 receptor (TR) α-expressing cells.<bold>Methods: </bold>We performed next-generation RNA sequencing on whole blood samples from eight athyroid patients (four females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene coexpression network analysis (WGCNA) was applied to identify thyroid state-related networks.<bold>Results: </bold>We detected 486 differentially expressed genes (fold-change >1.5; multiple testing corrected P value < 0.05), of which 76% were positively and 24% were negatively regulated. Gene ontology (GO) enrichment analysis revealed that three biological processes were significantly overrepresented, of which the process translational elongation showed the highest fold enrichment (7.3-fold, P = 1.8 × 10-6). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO analysis suggested that thyroid state affects platelet function.<bold>Conclusions: </bold>Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRα-expressing leukocytes. In addition, TH may regulate gene transcripts in platelets.
- Subjects
BLOOD platelets; CELL receptors; COMPARATIVE studies; GENES; RESEARCH methodology; MEDICAL cooperation; PROGNOSIS; RESEARCH; THYROID gland; THYROXINE; EVALUATION research; GENE expression profiling; SEQUENCE analysis
- Publication
Journal of Clinical Endocrinology & Metabolism, 2017, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2017-01144