Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Sex-biased Expression of Pharmacogenes Across Human Tissues

Version 1 : Received: 25 June 2021 / Approved: 28 June 2021 / Online: 28 June 2021 (15:08:38 CEST)

How to cite: Idda, M.L.; CAMPESI, I.; Fiorito, G.; Vecchietti, A.; Urru, S.A.M.; Solinas, M.G.; Franconi, F.; Floris, M. Sex-biased Expression of Pharmacogenes Across Human Tissues. Preprints 2021, 2021060675 (doi: 10.20944/preprints202106.0675.v1). Idda, M.L.; CAMPESI, I.; Fiorito, G.; Vecchietti, A.; Urru, S.A.M.; Solinas, M.G.; Franconi, F.; Floris, M. Sex-biased Expression of Pharmacogenes Across Human Tissues. Preprints 2021, 2021060675 (doi: 10.20944/preprints202106.0675.v1).

Abstract

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. Also, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We have detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (Liver, Lung, Kidney, Small intestine terminal ileum, Skin not sun-exposed, and Whole Blood). Among them, as expected, we observed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response related genes, reinforce the need to overcome the sex bias of clinical trials.

Subject Areas

pharmacogenes; transcripts; sex-bias; drug metabolism; sex differences

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