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

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 C0 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^*1A patients and non-PXR^*1A 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.