POR*28基因多态性与中国肾移植患者他克莫司稳定剂量的相关性研究

目的：探讨POR*28单核苷酸多态性（SNP）与中国肾移植患者他克莫司稳定剂量的相关性，为制定该人群个体化剂量调整方案提供参考。方法：共纳入350例中国肾移植患者，CYP3A5*3和POR*28基因检测由生工生物工程（上海）股份有限公司采用Mass ARRAY Analyzer Compac质谱检测。酶放大免疫测定法（EMIT）测定他克莫司血药谷浓度。分析上述基因型与他克莫司稳定剂量的相关性。结果：CYP3A5*3、POR*28等位基因频率均符合Hardy-Weinberg遗传平衡。CYP3A5*3 GG基因型肾移植患者稳定剂量比AG和AA基因型患者显著降低。基于CYP3A5分层分析，在CYP3A5表达与不表达组中，POR不同基因型均与他克莫司稳定剂量有显著相关性。至少携带一个T等位基因的POR*28患者的他克莫司的平均稳定剂量与携带CC野生型的患者之间差异均具有统计学意义（P=0.003 7和P=0.003 1）。多重线性回归分析显示，CYP3A5*3与POR*28基因分别可以解释36.6%与1.7%他克莫司稳定剂量个体化差异。结论：中国肾移植受者CYP3A5*3和POR*28基因型与他克莫司稳定剂量显著相关，移植前进行检测将有助于他克莫司的临床个体化用药。

Associations of POR*28 polymorphisms with tacrolimus stable dose in Chinese kidney transplantation patients

AIM: To investigate the correlation between POR*28 single nucleotide polymorphism (SNP) and tacrolimus stable dose in Chinese kidney transplant patients, and to provide reference for the development of individualized dose adjustment programs in this population. METHODS: A total of 350 Chinese kidney transplant patients were enrolled. CYP3A5*3 and POR*28 genes were detected by Mass ARRAY Analyzer Compac Mass spectrometry in Shenggong Bioengineering (Shanghai) Co., LTD. Serum trough concentration of tacrolimus was determined by ENZYME amplification immunoassay (EMIT). The correlation between the above genotypes and tacrolimus stable dose was analyzed. RESULTS: The frequencies of CYP3A5*3 and POR*28 alleles were consistent with hardy-Weinberg genetic balance. The stable dose in patients with CYP3A5*3 GG genotype was significantly lower than that in patients with AG and AA genotype. Based on stratified analysis of CYP3A5, different POR genotypes were significantly correlated with the stable dose of tacrolimus in CYP3A5 expression and non-expression groups. The mean stable dose of tacrolimus was statistically significant between POR*28 patients with at least one T allele and CC wild-type patients (P=0.003 7 and P=0.003 1). Multiple Regression Analysis showed that CYP3A5*3 and POR*28 explained 36.6%and 1.7%of the individual differences in stable doses of Tacrolimus, respectively. CONCLUSION: CYP3A5*3 and POR*28 genotypes are significantly correlated with tacrolimus stable dose in Chinese kidney transplant recipients, and detection before transplantation will contribute to clinical individualized tacrolimus medication.