关键词: 他克莫司, 基因多态性, POR*28, 肾移植

Abstract: 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.

Key words: tacrolimus, single nucleotide polymorphism, POR*28, kidney transplantation