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

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。

Influence of IL-10 and CYP3 A5 gene polymorphisms on the dose-adjusted trough blood concentrations of tacrolimus in Chinese renal transplant recipients during the stable period

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.