EFFECT OFVARIATIONSIN ABCC2, CYP2C9, CYP2C19 & SCN2A GENESON TREATMENT RESPONSETO ANTICONVULSANTS- A SYSTEMATIC REVIEWAND META-ANALYSIS OF GENETIC ASSOCIATION STUDIES

Abstract

Objective: This study was aimed to determine the effect of genetic polymorphisms (non-synonymous, missense, and copy number variations) in ABCC2, CYP2C9, CYP2C19&SCN2A genes on treatment response to anticonvulsants. Methods: The search was carried out in PubMed, Scopus, Cochrane Central Register of Controlled Trials, Embase, LILACS, Google Scholar, MEDLINE, ScienceDirect, Web of Science, and the DOAJ database. Hardy Weinberg Equilibrium (HWE), New-Castle Ottawa scale value, Cochrane Review Manager 5.0 (&R 4.0.3,) and Rayyan QCRI are used for assessing data synthesis, risk of bias, heterogeneity assessment using I[2]statistics and calculating Inter-rater agreement respectively. Publication bias assessment was performed using Eggers test and the Funnel plot. For statistical analysis, random effects modeling was used to explain the association between genetic variations in ABCC2, CYP2C9, CYP2C19 & SCN2A genes related to drug resistance or treatment failure. Results: This meta-analysis includes a total of 29 studies. We found a greater risk of AED resistance in ABCC2rs2273697 genetic variations (OR=1.51 [ 0.93-2.47], p value=0.03 at 95% CI), ABCC2 rs3740066 genetic variation has a greater possibility of AED resistance was seen in pooled population (OR= 0.85 [0.12-5.85], p-value<0.01 at 95% CI), risk of drug resistance was increased by ABCC2 rs717620 polymorphism. (OR =2.13, [1.02-4.44], p-value<0.01 at 95% CI), CYP2C9 rs1799853 polymorphism had a significant increase in AED resistance (OR =1.27, [0.49-3.32] p-value<0.01 at 95% CI), CYP2C9 rs1057910 polymorphism. (OR= 0.74, [0.32-1.70] p-value 0.01 at 95% CI), CYP2C19 rs4244285 polymorphism. (OR= 0.68, [0.29-1.62], p value=0.02 at 95% CI), SCN2A rs2304016 polymorphism. (OR= 1.20, [0.48-3.05], p value<0.01 at 95% CI), SCN2Ars17183814 polymorphism. (OR =1.51, [1.12-2.03], p value=0.30 at 95% CI). Conclusions:Gene polymorphisms play a key role in epilepsy development and therapeutic efficacy, and could have greater impact treatment outcomes.