孕烷X受体1792A>G及1944T>C等位基因对肾移植术后早期环孢素血药浓度的影响

Correlation Study of PXR 1792A>G and 1944T>C Genotypes with the Concentration/Dose Ratios of Cyclosporine in Renal Transplantation Subjects

目的探讨孕烷X受体1792A>G及1944T>C等位基因对中国肾移植患者术后早期环孢素谷浓度(C0/D)及峰浓度(C2/D)的影响。方法采用PCR-直接测序技术分析80例肾移植患者1792A>G及1944T>C等位基因类型,采用酶增强免疫测定技术测定患者C0及C2值。结果本研究中患者1792A>G及1944T>C等位基因频率分别为0.50和0.51,均符合Hardy-Weinberg平衡。二者之间表现为强烈连锁不平衡。术后第3周1792A>G及1944T>C与患者环孢素C0/D值显著相关,1792AA型患者和1944TT型患者C0/D值均高于突变型患者。3种单倍型患者CsA C0/D值在移植术后第3周亦存在显著性差异,GC型及AG-TC型患者CsA C0/D仅为AT型患者的80.20%及78.60%。PXR*1A簇患者的CsA血药浓度与非PXR*1A簇患者相比无统计学差异。未观察到1792A>G及1944T>C等位基因对环孢素C2/D的影响。结论1792A>G及1944T>C基因型与环孢素C0/D值显著相关,移植前对这2个等位基因进行检测将有利于环孢素给药剂量的调整。

OBJECTIVE To approach the effect of pregnane X receptor （PXR） 1792A〉G and 1944T〉C genotypes on serum cyclosporine （CsA） dose adjusted blood concentrations （C0/D and C2/D） in Chinese renal transplant recipients during the early stage following surgery. METHODS A total of 80 renal transplant recipients receiving CsA were genotyped by PCR-direct sequencing. The CO and C2 of CsA were determined by EMIT. RESULTS The allele frequencies of 1792A 〉G and 1944T〉C were 0.50 and 0.51, which fitted Hardy-Weinberg equilibrium. The 1792A〉G and 1944T〉C alleles exhibited linkage disequilibrium. There was a significant relationship between the two alleles and CsA C0/D after transplantation. The C0/D of 1792AA and 1944TT patients were marked higher than of other genotype patients, respectively. The haplotypes GC and AG-TC were also found to have a marked lower C0/D compared with haplotype AT patients, 80.20% and 78.60%, respectively. Haplotype cluster analysis revealed that there was no significantly difference of both CsA C0/D and C2/D between PXR＊IA patients and non-PXR＊IA patients. Neither polymorphisms nor haplotypes of 1792A〉G and 1944T〉C alleles statistically affected CsA C2/D. CONCLUSION The data suggest that 1792A〉G and 1944T〉C alleles affect CsA C0/D in Chinese renal transplant patients. Determination of the two alleles is benefit for adjusting CsA dosage.