Context: 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. Objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of T3 receptor (TR) a-expressing cells. Methods: 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. Results: 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 3 1026). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO analysis suggested that thyroid state affects platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRa-expressing leukocytes. In addition, TH may regulate gene transcripts in platelets.

Additional Metadata
Persistent URL dx.doi.org/10.1210/jc.2017-01144, hdl.handle.net/1765/111333
Journal Journal of Clinical Endocrinology and Metabolism
Citation
Massolt, E.T, Meima, M.E, Swagemakers, S.M.A, Leeuwenburgh, S, Van Den Hout-Van Vroonhoven, M.C.G.M. (Mirjam C. G. M.), Brigante, G. (Giulia), … Edward Visser, W. (2018). Thyroid state regulates gene expression in human whole blood. Journal of Clinical Endocrinology and Metabolism, 103(1), 169–178. doi:10.1210/jc.2017-01144