Metabolomik: Open Access

Sex Dependency of Human Metabolic Profiles Revisited

Abstract

Sabine Siegert, Zhonghao Yu, Rui Wang-Sattler, Thomas Illig, Jerzy Adamski, Stefan Schreiber, Michael Krawczak, Michael Nothnagel and Ute Nöthlings

Background: Human metabolic profiles based on the four compound classes acylcarnitines, amino acids, hexoses and phospho and sphingolipids were found to exhibit a significant sex difference in a previous study. We set out to verify this result in a geographically distinct cohort with an adequately sized sample by analyzing the same set of biomarkers and various additional biogenic amines not hitherto considered in such studies. Methods: The study population comprised 165 individuals (101 males, 64 females) for whom the serum concentrations of 138 different metabolites were measured. Sex differences were analyzed both at the level of individual metabolites by linear regression analysis and at the level of joint consideration of metabolites by partial least-squares discriminant analysis (PLS?DA). Results: The concentration of 60 metabolites (43.5%) showed a nominally significant sex difference in a linear regression analysis, 11 of which (8.0%) remained significant after correction for multiple testing. Among the previously studied markers, the most significant sex dependency was observed for lyso-phosphatidylcholine acyl C18:2 (adjusted p=0.001) and octadecadienyl-L-carnitine (p=0.004). Among the newly analyzed biogenic amines, only creatinine (adjusted p<10-4) and total dimethylarginine (p=0.017) showed a significant sex difference. PLS-DA confirmed the sex dependency of metabolic profiles. Conclusion: Various previously reported sex differences in human serum metabolite concentration were confirmed in an independent and slightly different cohort. In addition, the concentrations of at least two biogenic amines were found to be sex-dependent as well. In the light of an increased interest in and an increased availability of large-scale metabolic data, our study strongly emphasizes the need for sex stratification or sex adjustment in epidemiological and molecular studies based upon such profiles.