| Objective1.The study is to analyaze transporters(MDR1 C3435 T,C1236T,G2677T/A),metabolic enzyme cytochrome P450(CYP3A4*1B)and related receptors(progesterone receptor PGR,estrogen receptor ESR1,oxytocin receptor OXTR)gene polymorphism,mifepristone and its active metabolite N-demethyl mifepristone in the different early medical abortion patients,which is expected to reveal the source of the individual differences of mifepristone,and to select drugs and dosages more accurately,improve curative effect,reduce the occurrence of adverse reactions,and achieve mifepristone’s "individualized medication." Methods132 cases with early medical abortion who were treated with a combination of mifepristone and misoprostol were included in patients.Polymerase chain reaction(PCR)and Mass ARRAY molecular weight array technology were used to analyze MDR1 C3435 T and MDR1 C1236 T,MDR1 G2677T/A,CYP3A4*1B,PGR,ESR1 and OXTR for SNP typing.Liquid chromatography/tandem mass spectrometry(LC-MS/MS)determined the plasma concentration of mifepristone and its active metabolite,N-demethyl mifepristone,to observe and compare the efficacy of drug abortion and the incidence of adverse reactions.Results1.In this study,the success rate of mifepristone combined with misoprostol in the treatment of early medical abortion was 81.06%,the incidence of adverse reactions was 90.91%.The failure of medical abortion was significantly related to the patient’s gestational sac diameter,uterine position,cesarean section and abortion history;the occurrence of adverse reactions was obviously related to the patient’s weight,pregnancy history and cesarean section history.The plasma concentration-dose ratio(C/D)of mifepristone and its active metabolite N-demethyl mifepristone in the successful medical abortion group and the adverse reaction group was significantly higher than that of the failed medical abortion group and no adverse effects Response group(P<0.05).2.In this study,there were 132 patients MDR1 3435C→T,MDR1 1236 C→T,MDR1 2677G→T/A CYP3A4 C→T,CYP3A4*1B C→T,PGR(rs1042838)C→A,PGR(rs10895068)C → T,ESR1 G → A,OXTR(rs2254298)G → A,OXTR(rs2228485)G→A,OXTR(rs237911)G→A,OXTR(rs53576)A→G mutation frequencies were 31.82% and 61.74%,respectively,48.11%,31.44%,97.35%,1.14%,0,26.14%,69.32%,72.73%,73.11% and 70.83%.3.Carrying OXTR(rs2254298)mutant allele A,OXTR(rs2228485)mutant allele A,OXTR(rs237911)mutant allele A and OXTR(rs53576)mutant allele G significantly increase the risk of miscarriage failure in early abortion patients(P<0.05).Carrying MDR1 C3435 T mutant allele T,MDR1 G2677T/A/A mutant allele T/A,OXTR(rs2254298)mutant allele A,OXTR(rs2228485)mutant allele A,OXTR(rs237911)mutant allele A and OXTR(rs53576)mutant allele G significantly increased the risk of adverse reactions in patients with early medical abortion(P<0.05).4.The plasma concentration dose ratio(C/D)of patients with wild-type(GG)genome in MDR1 G2677T/A was significantly higher than that of mutant genome(P<0.05),and in CYP3A4 C>T patients with wild-type(CC)genome The drug concentration-dose ratio(C/D)was significantly higher than that of the mutant genome(CT+TT)(P<0.05).Conclusion1.OXTR(rs2254298 G>A),OXTR(rs2228485 G>A),OXTR(rs237911 G>A)and OXTR(rs53576 A>G)gene mutations can increase the failure rate of early medical abortion and the incidence of adverse reactions with mifepristone.2.MDR1 C1236T(C>T)and MDR1 G2677T/A(G>T/A)gene mutations can increase the incidence of adverse reactions during early medical abortion of mifepristone.3.The plasma concentration of mifepristone and its active metabolite N-desmethylmifepristone is related to the efficacy and adverse reactions of early medical abortion.4.MDR1 G2677T/A(G>T/A)gene mutation can reduce the plasma concentration of mifepristone and its active metabolite N-desmethylmifepristone,CYP3A4(C>T)gene mutation can significantly reduce the blood concentration of mifepristone,thereby affecting its curative effect. |
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