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Published on: December 31, 2017
Influence of Sex on Urinary Organic Acids: A Cross-Sectional Study in Children
Marianna Caterino1,2, Margherita Ruoppolo1,2, Guglielmo Rosario Domenico Villani1,2
1Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', 80131 Napoli, Italy.
Insights
Urinary organic acid levels differ significantly between males and females, with these sex differences varying by age and impacting metabolic pathways. Personalized medicine may require sex- and age-specific reference values.
Area of Science:
- Metabolomics
- Pediatric Research
- Personalized Medicine
Background:
- Urinary metabolome analysis is crucial for personalized medicine, reflecting individual physiological states.
- Factors like sex and age significantly influence urinary metabolite profiles.
- Understanding these influences is key to interpreting metabolic data accurately.
Purpose of the Study:
- To investigate sex-based differences in 72 urinary organic acids in children aged 1-36 months.
- To determine how these sex differences vary across different age groups.
- To identify specific metabolic pathways affected by sex and age.
Main Methods:
- Gas chromatography-mass spectrometry (GC-MS) analysis of urine samples.
- Study cohort: 291 children (152 males, 139 females) aged 1-36 months.
- Data stratified by age into four groups to analyze sex-specific trends.
Main Results:
- Specific organic acids were exclusively found in males (e.g., 4-hydroxy-butyrate) or females (e.g., phenylacetate).
- Sex differences were more pronounced in infants under 6 months old.
- Key affected pathways included mitochondrial homeostasis, citrate cycle, and amino acid metabolism, with distinct patterns in males and females.
- Age influenced metabolic pathways differently between sexes, notably phenylalanine metabolism in males.
Conclusions:
- Sex profoundly impacts both the quantity and type of urinary organic acids, with age-dependent variations.
- Sex-specific and age-stratified reference values for urinary organic acids may be necessary for accurate clinical interpretation.
- These findings underscore the importance of considering sex and age in metabolomic studies for personalized health approaches.
Abstract:
The characterization of urinary metabolome, which provides a fingerprint for each individual, is an important step to reach personalized medicine. It is influenced by exogenous and endogenous factors; among them, we investigated sex influences on 72 organic acids measured through GC-MS analysis in the urine of 291 children (152 males; 139 females) aging 1-36 months and stratified in four groups of age. Among the 72 urinary metabolites, in all age groups, 4-hydroxy-butirate and homogentisate are found only in males, whereas 3-hydroxy-dodecanoate, methylcitrate, and phenylacetate are found only in females. Sex differences are still present after age stratification being more numerous during the first 6 months of life. The most relevant sex differences involve the mitochondria homeostasis. In females, citrate cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate, glutamate, and butanoate metabolism had the highest impact. In males, urinary organic acids were involved in phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, butanoate metabolism, and glyoxylate and dicarboxylate metabolism. In addition, age specifically affected metabolic pathways, the phenylalanine metabolism pathway being affected by age only in males. Relevantly, the age-influenced ranking of metabolic pathways varied in the two sexes. In conclusion, sex deeply influences both quantitatively and qualitatively urinary organic acids levels, the effect of sex being age dependent. Importantly, the sex effects depend on the single organic acid; thus, in some cases the urinary organic acid reference values should be stratified according the sex and age.
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