B-vitamin-associated miRNAs are enriched in pathways related to cell proliferation - insights from the general population

Abstract Background Vitamins are essential micronutrients that play crucial roles in human health, including immune function, cell development, energy metabolism, and the function of the nervous system. Within the body, vitamins can activate and modulate various biological pathways by acting as cofactors for enzymes. The objective of this study was to identify microRNAs (miRNAs) associated with the serum concentration of specific vitamins in the general population, and subsequently identifying vitamin associated biological systems and diseases potentially influenced by post-transcriptional regulation of these miRNAs. Methods Data from the population-based Study of Health in Pomerania (SHIP-TREND-0, N = 792) were utilized to examine the associations between vitamin B12 and folic acid (vitamin B9) and 181 miRNAs. Multivariate linear models were employed, adjusting for potential confounders such as age, sex, platelet count, BMI, hemolysis, batch effects, and seasonality. Publicly available databases were used to identify biological pathways influenced by those significant miRNAs. Results After correction for multiple comparisons, eight miRNAs were found to be positively associated with folic acid, and six miRNAs were positively associated with vitamin B12. The miRNAs significantly associated with folic acid were predominantly found in red blood cells, while those associated with vitamin B12 were associated with red blood cells and T-cells according to the miR-Blood database. Analyses of over-represented miRNAs revealed enrichment in processes related to cell-cycle regulation, DNA synthesis, metabolic processes, and erythropoiesis. In accordance to the known positive role of folic acid and vitamin B12 in pregnancy, nearly all significant miRNAs have been identified to be associated with pregnancy outcomes based on previous research. Conclusions The analyses revealed that several miRNAs are related to vitamin levels and that these miRNAs are associated with processes such as cell proliferation and human fertility. These miRNAs could be interesting targets for further clinical applications.