Sex-Biased Expression of Genes Allocated in the Autosomal Chromosomes: Blood LC-MS/MS Protein Profiling in Healthy Subjects

Abstract

Background. Sex and gender have a large impact in human health and disease prediction. According to genomic/genetics, men differ from women by a limited number of genes in Y chromosome, while the phenotypes of the 2 sexes differ markedly. Methods. In this study, serum samples from six healthy Bahraini men and women were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS). Bioinformatics databases and tools were used for protein/peptide (PPs) identification and gene localization. The PPs that differed significantly ( $p$  < 0.05, ANOVA) in abundance with a fold change (FC) of ≥1.5 were identified. Results. Revealed 20 PPs, 11 were upregulated in women with very high FC (up to 8 folds), and 9 were upregulated in men but with much lower FC. The PPs are encoded by genes located in autosomal chromosomes, indicative of sex-biased gene expression. The only PP related to sex, the sex hormone-binding globulin, was upregulated in women. The remaining PPs were involved in immunity, lipid metabolism, gene expression, connective tissue, and others, with some overlap in function. Conclusions. The upregulated PPs in men or women are mostly reflecting the functon or risk/protection provided by the PPs to the specific sex, e.g., Apo-B100 of LDLC. Finally, the basis of sex-biased gene expression and sex phenotypic differences needs further investigation.