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| CYP3A5、MDR1基因多态性对他克莫司治疗后膜性肾病患者临床疗效和感染并发症的影响 |
| Influence of CYP3A5 and MDR1 gene polymorphisms on clinical efficacy and infectious complications of patients with membranous nephropathy after tacrolimus treatment |
| 投稿时间：2023-08-15 |
| DOI：10.3969/j.issn.1000-0399.2024.12.003 |
| 中文关键词: 细胞色素P450酶3A5 多药耐药基因1 基因多态性 他克莫司 膜性肾病 |
| 英文关键词: Cytochrome P450 enzyme 3A5 Multidrug resistance gene 1 Gene polymorphism Tacrolimus Membranous nephropathy |
| 基金项目:河南省医学科技攻关联合共建项目（编号：2018020859） |
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| 中文摘要: |
| 目的 分析细胞色素P450酶3A5（CYP3A5）、多药耐药基因1（MDR1）基因多态性对他克莫司治疗后原发性膜性肾病（PMN）患者临床疗效和感染并发症的影响。方法 选择2020年10月至2022年10月郑州市第七人民医院收治的PMN患者75例，采用限制性片段长度多态性聚合酶链反应（PCR-RFLP）方法检测CYP3A5*3、MDR1 C1236T、MDR1 G2677T、MDR1 C3435T基因多态性，并比较不同基因型他克莫司C/D值（他克莫司血药浓度/剂量×体质量）差异以及对PMN患者临床疗效和感染并发症发生情况的影响。结果 CYP3A5*3中*3/*3基因型、G等位基因突变频率分别为54.67%和75.33%，MDR1 C1236T中CT基因型突变频率为57.33%，MDR1 G2677T中GT基因型突变频率为49.33%，MDR1 C3435T中CT基因型突变频率高达57.33%；CYP3A5*3中AA+AG基因型他克莫司C/D值低于GG基因型，差异有统计学意义（P<0.05），MDR1 C3435T中CC基因型他克莫司C/D值低于CT+TT基因型，差异有统计学意义（P<0.05）；CYP3A5*3、MDR1 C1236T/A、MDR1 G2677T不同基因型使用的他克莫司剂量对PMN患者临床疗效的影响差异无统计学意义（P>0.05），MDR1 C3435T中CT+TT基因型他克莫司治疗缓解率高于CC基因型（71.70%比45.45%，P<0.05），差异有统计学意义；CYP3A5、MDR1不同基因型使用的他克莫司剂量对PMN患者感染并发症发生率，差异无统计学意义（P>0.05）。结论 CYP3A5*3 GG基因型和MDR1 C3435T CT+TT基因型可升高他克莫司C/D值，且MDR1 C3435T CT+TT基因型患者他克莫司临床疗效较好。 |
| 英文摘要: |
| Objective To analyze the effects of cytochrome P450 enzyme 3A5 (CYP3A5) and multidrug resistance gene 1 (MDR1) gene polymorphisms on clinical efficacy and infectious complications in patients with primary membranous nephropathy (PMN) after tacrolimus treatment. Methods Totally 75 patients with PMN admitted to the 7th People’ s Hospital of Zhengzhou were enrolled between October 2020 and October 2022. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) method was used to detect the gene polymorphisms of CYP3A5*3, MDR1 C1236T, MDR1 G2677T and MDR1 C3435T, and the difference in C/D value (tacrolimus blood concen-tration/dose×body mass) of tacrolimus of different genotypes and the effects on clinical efficacy and occurrence of infectious complications in PMN patients were compared. Results The mutation frequencies of *3/*3 genotype and G allele in CYP3A5*3 were 54.67% and 75.33%, and the mutation frequency of CT genotype in MDR1 C1236T was 57.33%, and the mutation frequency of GT genotype in MDR1 G2677T was 49.33%, and the mutation frequency of CT genotype in MDR1 C3435T was as high as 57.33%. The C/D value of tacrolimus of AA+AG geno-type in CYP3A5*3 was lower than that of GG genotype (P<0.05), and the C/D value of tacrolimus of CC genotype in MDR1 C3435T was lower than that of CT+TT genotype (P<0.05). There were no statistically significant differences in the effects of tacrolimus dose used for different genotypes of CYP3A5*3, MDR1 C1236T/A, and MDR1 G2677T on the clinical outcome of patients with PMN (P>0.05). The remission rate of tacrolimus dose used in the CT+TT genotype in MDR1 C3435T was higher than that in the CC genotype (71.70% vs 45.45%, P<0.05). There were no statistical differences between tacrolimus doses used for different genotypes of CYP3A5 and MDR1 on the incidence of infectious complications in patients with PMN (P>0.05). Conclusion GG genotype of CYP3A5*3 and CT+TT genotype of MDR1 C3435T can increase the C/D value of tacrolimus, and patients with CT+TT genotype of MDR1 C3435 T have better clinical efficacy of tacrolimus. |
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