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Relationships among biomarkers of one-carbon metabolism

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Abstract

One-carbon metabolism is a network of metabolic pathways, disruption of which has been associated with cancer and other pathological conditions. Biomarkers of these pathways include homocysteine (HCY), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). A better understanding of the relationships between these biomarkers is needed for their utilization in research. This study investigated the relationships between fasting concentrations of plasma HCY, SAM, SAH and the ratio of SAM:SAH, and serum folate, vitamin B12 and creatinine in a healthy adult population. A cross-sectional study recruited 678 volunteers; only subjects with complete data (n = 581) were included in this analysis. Correlations were used to examine bivariate relationships among the biomarkers and multivariate linear regression determined independent relationships with HCY, SAM and SAH treated as dependent variables in separate models. Multivariate logistic regression examined determinants of a low SAM:SAH ratio (defined as having a SAM:SAH ratio in the bottom quartile and SAH value in the top quartile). HCY correlated inversely with folate and vitamin B12 and weakly correlated with SAH and creatinine. Both SAM and SAH correlated with creatinine but were independent of serum folate and vitamin B12. In multivariate analyses, folate, vitamin B12, creatinine, sex and age were associated with HCY; age and creatinine were determinants of SAM, and sex and creatinine determinants of SAH. Finally, male sex and increasing creatinine levels were associated with having a low SAM:SAH ratio. Findings suggest that HCY, SAM and SAH are relatively independent parameters and reflect distinct aspects of one-carbon metabolism.

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Acknowledgements

The authors would like to thank the study participants and study coordinator Gwyneth Fairfield. This research was supported by an operating grant from the Canadian Institutes of Health Research.

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Correspondence to Will D. King.

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King, W.D., Ho, V., Dodds, L. et al. Relationships among biomarkers of one-carbon metabolism. Mol Biol Rep 39, 7805–7812 (2012). https://doi.org/10.1007/s11033-012-1623-y

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