Interethnic DNA Methylation Difference and its Implications in Pharmacoepigenetics

What is it about?

DNA methylation, in which methyl groups are added to the C-5 position of the cytosine ring in the CpG dinucleotide of DNA, is a major epigenomic mechanism. In contrast to genomic mechanisms, DNA methylation influences phenotypes (e.g., drug response and ADME) without any involvement of the DNA sequence change. Therefore, DNA methylation provides an additional phenotype variation. Numerous studies have demonstrated that interethnic differences in the genomic makeup influence the drug response and ADME. Ethnic differences have also been found in DNA methylation; however, the influence of interethnic DNA methylation differences on the drug response and ADME remains largely unknown. In this study, we identified E-CpG sites and found that some of them were related to the drug response and ADME. We found evidence that some of the E-CpG sites triggered differential gene expression and influenced the drug response and ADME in different populations. For example, the results of cg27560818 on SLC7A5 were combined with the finding of genomic studies to explain the poor response to tamoxifen therapy in African ancestry patients. Our findings demonstrated that the ethnic effects on pharmacoepigenetics and the patterns may change according to tissue types. Applying the right treatment and right dosage to the patients from the ethnic population is critical in clinical practice and pharmacoepigenetics research.

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Why is it important?

This is the first systematic study to examine the population differentiation effect of DNA methylation on the treatment response and drug ADME in multiple tissue types and cancer types. The results provide evidence about the influence of interethnic differences in DNA methylation on differential gene regulation and pharmacoepigenetics by tissue types.

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