Method
Search strategy
We searched the Pubmed and Embase exhaustively about what and how individual factors influence the DNA methylation of genes related to drug metabolism. Searches used the following title, abstract, keyword and Medical Subject Headings (MeSH) terms: (1) DNA methylation; (2) genes related to drug metabolism; (3) influence, related, affect, factors. Reference lists of identified articles and reviews were also searched for additional references. The search and filtering process was done under the supervision of senior researchers.
Selection criteria
The studies were selected for inclusion if they fulfilled the following criteria: (1) published from 2000 onwards. (2) published in English. (3) experiments about people, mice or cells. (4) genes were involved in metabolism. The reason why we choose experiment about people, mice and cells was that we need findings to be used in clinical treatment. We excluded the DNA methylation related to diseases because these genes were often part of disease pathogenesis, hardly involved in metabolism, and nearly have no influence on drug metabolism. Each reviewer screened part of the publications independently with the inclusion and exclusion criteria and inter-reviewer disagreement was discussed and resolved by a senior author. More details are in Fig.1 about the selection process.
Data extraction
For the papers included, we extracted following information.
Information was recorded by two authors independently and any disagreement were discussed and resolved by a senior author. Complete records were aggregated in appendix.