3.2.1 Associations between ABCB1 (c.3435C>T), EPHX1 (c.337T>C and c.416A>G), SCN1A (c.3184A>G and IVS5-91G>A) polymorphisms and CBZ metabolism.
For ABCB1 c.3435C>T polymorphism, a total of 714 epilepsy patients treated by CBZ in 4 studies [8, 29, 31, 33] were included, and a statistically significant association was found in the (CC vs CT)model for the adjusted concentrations of CDRCBZ(OR = 0.251 (95% CI: 0.081~0.42), P = 0.004)(Table 3) (Fig. 2). For ABCB1 c.2677G>T/Apolymorphism, a total of 569 epilepsy patients treated by CBZ in 3 studies were included, and a statistically significant association was found in the (GG vs GA) model for the adjusted concentrations of CDRCBZ (OR = -0.366 (95% CI: -0.697~-0.036), P = 0.030) with high heterogeneity (I2=64.2%)(Table 3). There is no significant association between other genetic models in ABCB1 c.3435C>T and ABCB1 c.2677G>T/A [29, 31, 33] (3 studies including 569 epilepsy patients) and the whole genetic models in c.1236C>T [29, 31-33] (4 studies including 659 epilepsy patients) polymorphisms on the adjusted concentrations of CDRCBZ (Table 3).
For EPHX1 c.416A>G polymorphism, the adjusted concentrations of CDRCBZ, CDRCBZE and CDRCBZD were reported in 4 [7, 8, 25, 31], 3 [7, 8, 31] and 3 [7, 8, 31] articles, respectively. A total of 646 epilepsy patients treated by CBZ in 3 studies were included with statistically significant association between (AA vs GG) ,(AG vs GG) models in EPHX1 c.416A>Gpolymorphisms and CDRCBZD (OR = 0.483 (95% CI: 0.011~0.956), P = 0.045; OR = 0.682 (95% CI: 0.163~1.201), P = 0.010, respectively) (Table 3) (Fig. 3). No association was observed between other genetic models ofEPHX1 c.416A>G polymorphism and on the adjusted concentrations of CDRCBZ, CDRCBZE, CDRCBZD, respectively (Table 3).
For EPHX1 c.337T>C polymorphisms, the adjusted concentrations of CDRCBZ, CDRCBZE, CDRCBZD, CDRCBZE : CDRCBZ and CDRCBZD : CDRCBZE including 812 epilepsy patients were reported in 4 [7, 8, 25, 31], 3 [7, 8, 31], 3 [7, 8, 31], 3 [7, 8, 17] and 3 [7, 8, 31] articles, respectively. A statistically significant association was found in the (TT vs CC) model for the adjusted concentrations of CDRCBZE (OR = -0.446 (95% CI: -0.811~-0.0.081), P = 0.004) with high heterogeneity (I2=98.9%) (Table 3). No significant association among other genetic models of EPHX1 c.337T>C polymorphism and on the adjusted concentrations of CDRCBZ, CDRCBZE, CDRCBZD, CDRCBZE : CDRCBZ and CDRCBZD : CDRCBZE were found (Table 3).