IL-10和CYP3A5基因多态性对中国肾移植病人术后稳定期他克莫司血药浓度/剂量比的影响

陈昭琳; 方焱; 程希; 冯晓俊; 张蕾; 唐丽琴

doi:10.13898/j.cnki.issn.1000-2200.2021.07.001

IL-10和CYP3A5基因多态性对中国肾移植病人术后稳定期他克莫司血药浓度/剂量比的影响

Influence of IL-10 and CYP3A5 gene polymorphisms on the dose-adjusted trough blood concentrations of tacrolimus in Chinese renal transplant recipients during the stable period

摘要

摘要:
目的探讨白细胞介素10(IL-10)和CYP3A5基因多态性对中国汉族肾移植病人术后稳定期他克莫司血药浓度/剂量比(C₀/D)的影响。
方法以随访的149例稳定期肾移植病人作为研究对象，采用竞争性等位基因特异性PCR检测IL-10-819 C/T、-592 C/A、-1082 G/A和CYP3A5 6986 A/G基因分型。采用化学发光免疫分析法测定他克莫司的血药谷浓度(C₀)，比较IL-10和CYP3A5基因多态性对他克莫司C₀/D的影响。
结果在149例肾移植稳定期病人中，IL-10-592 C/A、-1082 G/A基因多态性对他克莫司C₀/D均没有明显影响；而-819C/T与他克莫司C₀/D存在明显相关性，IL-10-819 TT型他克莫司C₀/D均明显高于TC/CC型(P < 0.05)。同时CYP3A5 6986 GG型(无活性组)的他克莫司C₀/D明显高于CYP3A5 6986 GA/AA型(有活性组)(P < 0.05)。进一步分析后发现，在CYP3A5有活性组中，IL-10-819 TT型病人的他克莫司C₀/D明显高于IL-10-819 TC/CC型病人(P < 0.05)；在CYP3A5无活性组中，IL-10-819 TT型病人他克莫司C₀/D也明显高于IL-10-819 TC/CC型病人(P < 0.05)。
结论在肾移植术后稳定期，IL-10-819 C/T和CYP3A5 6986 A/G基因多态性与他克莫司C₀/D具有明显相关性，且IL-10-819 TT型对CYP3A5 6986 GG型病人的他克莫司C₀/D影响最大。

Abstract:
ObjectiveTo investigate the influence of interleukin 10(IL-10) and CYP3A5 genetic polymorphism on the dose-adjusted trough blood concentrations(C₀/D) of tacrolimus in Chinese renal transplant recipients during the stable period.
MethodsA total of 149 renal transplant recipients were enrolled in the analysis.Kompetitive allele specific PCR was used to detect the IL-10-819 C/T, -592 C/A, -1082 G/A and CYP3A5 6986 A/G gene polymorphisms.Tacrolimus trough level(C₀) was determined by chemiluminesent immunoassay assay.
ResultsAmong 149 renal transplant patients, IL-10-592 C/A and -1082 G/A gene polymorphisms had no significant effect on C₀/D of tacrolimus.But there was a significant correlation between -819C/T and tacrolimus C₀/D, C₀/D of tacrolimus for patients with IL-10-819 TT was higher than that of those with -819 TC/CC(P < 0.05).And C₀/D of tacrolimus in the CYP3A5 non-expressing group(6986 GG genotype) was higher than those in the CYP3A5 expressing group(6986 GA/AA genotype)(P < 0.05).Moreover, C₀/D of tacrolimus of IL-10-819 TT genotype was higher than that of -819 TC/CC genotype in the CYP3A5 expressing group, which showed the similar results in the CYP3A5 non-expressing group(P < 0.05).
ConclusionsIL-10-819 C/T and CYP3A5 6986 A/G gene polymorphisms are associated with the C₀/D of tacrolimus in renal transplant patients during the stable period, and IL-10-819 TT has the greater effect on the C₀/D of tacrolimus in CYP3A5 6986 GG patients.

HTML全文

参考文献(25)

施引文献

资源附件(0)