Effect of gene polymorphisms of multidrug resistance gene 1 and
cytochrome P450 3A4 on the blood concentration and efficacy of
mifepristone in medical abortion
Abstract
Objectives: We aim to exploring the association among the gene
polymorphisms of multidrug resistance gene 1 (MDR1) and cytochrome P450
3A4 (CYP3A4), the blood concentration of mifepristone and the outcomes
of mifepristone in medicine abortion, in order to developing an
individualized treatment of mifepristone. Methods: 126 patients of
medicine abortion were enrolled, which received a regimen of
mifepristone and misoprostol. The blood concentration of mifepristone
and monodemethyl-mifepristone was detected by LC-MS/MS analysis.
Polymorphisms of MDR1 3435C>T, 1236C>T,
2677G>T/A and CYP3A4*1G were genotyped by MassARRAY
technology. Results: The patients in successful outcome group have a
higher blood concentration of both mifepristone and
monodemethyl-mifepristone than that in failed outcome patients (P =
0.031 and 0.012, respectively). Meanwhile, there was a relationship
between the C/D ratio of mifepristone, monodemethyl-mifepristone and the
efficacy of mifepristone (P = 0.040 and 0.017, respectively). In
addition, the occurrence of adverse reaction of mifepristone was
associated with a higher blood concentration of mifepristone as well as
C/D ratio of mifepristone (P = 0.010 and 0.008, respectively). MDR1
G2677T/A was linked with the C/D ratio of mifepristone and
monodemethyl-mifepristone (P = 0.012 and 0.004, respectively), as well
as the efficacy and adverse reaction of mifepristone (P = 0.042 and
0.001, respectively). CYP3A4*1G genotype was related with a lower blood
concentration of mifepristone (P = 0.012). Conclusion: The blood
concentration of mifepristone and monodemethyl-mifepristone and MDR1
2677G>T/A could be a reliable indicator in a successful
outcome of mifepristone for medicine abortion and the occurrence of
adverse reaction.