Association of zinc level with DNA methylation and its consequences: A systematic review

BACKGROUND: DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in DNA methylation. Therefore, abnormal zinc levels may cause aberrant DNA methylation and other diseases. OBJECTIVES: To investigate the influence of zinc on gene-specific and global DNA methylation in humans and rodents, their tissues and their cells. METHOD: Systematic literature searches were conducted using Medline, Scopus, Google Scholar, and Web of Science databases. Studies that met the inclusion criteria and were published in English language were included. Data including the first author, sample size, subjects, targeted genes, tissue types or cells analysed, zinc level, molecular techniques, DNA methylation outcomes, and consequences were extracted. RESULTS: From a total of 2360 articles screened by title and abstract, 15 met the inclusion criteria. Qualitative analysis indicates that there are associations between zinc deficiency and gene-specific hypomethylation in humans and between zinc deficiency and hypermethylation in rodents. Zinc did not influence LINE-1 methylation in humans. Depending on cell type, zinc could have a positive or negative effect on global methylation in humans and rodents. As predicted, in general, gene expression was elevated by DNA hypomethylation and the corresponding protein levels were also upregulated. However, some studies showed that zinc deficiency led to reduced gene expression or no alteration in mRNA levels and corresponding protein levels. CONCLUSION: Our study shows links between zinc levels and DNA methylation. However, greater significance may be achieved if more than one independent investigator analyses the same set of genes in the same cell type. Therefore, gene-cell and animal-specific investigations are recommended to reduce variability and allow comparisons across studies.