ABCB1 c.3435C>T and EPHX1 c.416A>G
polymorphisms influence plasma carbamazepine concentration, metabolism
and pharmacoresistance in epileptic patients
Abstract
Background: ABCB1, EPHX1 and SCN1A gene polymorphisms have been reported
play important roles in individual variability carbamazepine (CBZ)
metabolism and resistance, but the result of that association still
remains controversial. Objective: To clarify the associations among
ABCB1, EPHX1 and SCN1A gene polymorphisms and CBZ metabolism and
resistance. Methods: 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 for appropriate studies up to April 2020. Results: A total
of 18 studies involving 3293 related epilepsy patients were included.
ABCB1 c.3435C>T polymorphism was significantly associated
with adjusted concentrations of CBZ (CC vs. CT, P=0.004), and EPHX
c.416A>G polymorphism was significantly associated with
carbamazepine-10, 11-trans dihydrodiol (CBZD) (AA vs. GG, P=0.045; AG
vs. GG, P=0.010). Furthermore, ABCB1 c.3435C>T polymorphism
was also observed to be significantly influenced CBZ resistance (CT vs
TT, P=0.01; CC+CT vs TT, P=0.006). Conclusion: ABCB1
c.3435C>T polymorphism may affect the CBZ metabolism and
resistance, EPHX1 c.416A>G polymorphism may only affect CBZ
metabolism. These findings provided further evidence for individualized
therapy of epilepsy patients in clinics. Nevertheless further large
studies are still warranted to provide conclusive evidences.