Abstract:
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.