2.1 Search and inclusion/exclusion criteria
The present systematic review was based on with the PRISMA statement principles [18]. The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology medicine disc and Wan Fang Database were searched up to 30 April 2020 using the boolean combination of the following key terms: “Carbamazepine” OR “ABCB1 ” OR “MDR1 ” OR “EPHX1 ” OR “SCN1A ” AND “polymorphism”. Eligible studies were required to meet the following inclusion criteria: (i) case–control studies; (ii) investigating the association of ABCB1 polymorphisms and or EPHX1polymorphisms and plasma concentration or resistance of CBZ in epileptic patients; (iii) reporting sufficient data for estimating an odds ratio (OR) for the association with the gene variants of interest; (ⅳ) each patient was administrated with CBZ monotherapy and not receiving pharmacological treatment for other pathologies; (ⅴ) including at least 3 studies for each polymorphism to allow calculation of publication bias between studies.
Exclusion criteria: (i) review articles and editorials; (ii) duplication of previous publications; (iii) not human studies; (ⅳ) not English or Chinese articles. All potentially relevant studies retrieved in the initial screening step were then read in their entirety to assess appropriateness for inclusion in the systematic review. The reference lists of all included studies and relevant reviews were also checked to identify additional studies missed from the initial electronic search. The corresponding authors were contacted by e-mail when relevant data could not be extracted from the original paper. Studies were excluded if the corresponding author did not answer to the e-mail or was unable to provide the requested data. If two or more studies shared part of the same patient population, the one with the larger sample size was included. All studies were independently analysed by two reviewers and any discrepancies in data extraction were resolved through consensus.