CYP3A5和ABCB1基因多态性与肾移植术后服用他克莫司患者医院感染的关系

Relationship between CYP3A5,ABCB1polymorphisms and nosocomial infection in renal transplantation patients treated with tacrolimus

目的探究细胞色素P4503A5(CYP3A5)和腺苷三磷酸结合盒转运体B1(ABCB1)基因多态性与肾移植术后服用他克莫司患者医院感染的关系。方法选取2016年10月-2019年10月于郑州市第七人民医院接受肾移植,术后服用他克莫司+霉酚酸酯+强的松免疫抑制治疗的64例患者为研究对象,利用等位基因特异扩增法和测序法检测患者的CYP3A5、ABCB1C1236T(rs1128503)、ABCB1C3435T(rs1045642)基因型,根据术后是否发生医院感染分为感染组和非感染组,分析CYP3A5和ABCB1基因多态性与医院感染的关系。结果64例患者中有24例发生术后感染,感染率为37.50%,其中13例下呼吸道感染,6例泌尿道感染,5例血流感染;两组患者的CYP3A5和ABCB1基因型频率分布均符合Hardy-Weinberg平衡定律;感染组患者的ABCB1C1236T等位基因型和等位基因频率与非感染组比较差异有统计学意义(P<0.05),CYP3A5和ABCB1C3435T等位基因型、等位基因频率与非感染组比较差异无统计学意义;校正性别、年龄等因素后,Logistic回归分析结果显示:ABCB1C1236T的T等位基因与医院感染发生相关(P<0.05)。结论ABCB1C1236T多态性可能与肾移植术后服用他克莫司患者医院感染相关,突变等位基因位点T可能是风险等位基因。

OBJECTIVE To explore the relationship between cytochrome P4503A5(CYP3A5),ATP-binding cassette subfamily B member 1(ABCB1)polymorphisms and nosocomial infections in renal transplantation patients treated with tacrolimus.METHODS From Oct 2016to Oct 2019,a total of 64patients who received renal transplantation in the Zhengzhou Seventh People′s Hospital and were treated with tacrolimus,mycophenolate mofetil and prednisone for immunosuppressive therapy after the surgery were recruited as the study subjects.The genotypes of CYP3A5,ABCB1C1236T(rs1128503)and ABCB1C3435T(rs1045642)were detected by allele specific amplification and sequencing method.The enrolled patients were divided into the infection group and the non-infection group according to the status of postoperative nosocomial infection,and the association between the CYP3A5,ABCB1gene polymorphisms and the nosocomial infection was observed.RESULTS Among the 64patients,24had postoperative infection,with the infection rate 37.50%;there were 13cases of lower respiratory tract infection,6 cases of urinary tract infection and 5cases of bloodstream infection.The frequency distribution of CYP3A5and ABCB1genotypes of both groups was consistent with Hardy-Weinberg equilibrium law.There were significant differences in ABCB1C1236Tallele genotypes and allele frequencies between the infection group and the non-infection group(P<0.05);there were no significant differences in the CYP3A5,ABCB1C3435Tallele genotypes and allele frequencies between the infection group and the non-infection group.After the factors such as gender and age were adjusted,the result of logistic regression analysis showed that the T alleles of ABCB1C1236Twere associated with the nosocomial infection(P<0.05).CONCLUSIONThe polymorphisms of ABCB1C1236Tmay be related to the nosocomial infection in the renal transplantation patients treated with tacrolimus,the mutant allele locus T may be the risk allele.