Abstract:
OBJECTIVE To investigate the effect of vitamin D receptor(VDR) genetic polymorphism on the concentration of tacrolimus in renal transplant recipients at early stage after transplantation.
METHODS The 360 cases of renal transplant recipients who received tacrolimus, mycophenolic acid, and glucocorticoid were recruited.
CYP3A5(
rs776746) and
VDR(
VDR ApaI rs7975232,
VDR
BsmI rs1544410,
VDR FokI rs2228570 and
VDR TaqI rs731236) genotypes were determined. The differences of concentration(C), dose(D) and the ratio of concentration to dose(C/D) of tacrolimus were compared among all of the genotype groups at the seventh day after renal transplantation.
RESULTS The C and C/D of tacrolimus in
CYP3A5 non-expresser(GG genotype) were all significantly higher than
CYP3A5 expresser(AA and AG genotype)(
P<0.05). When taking the different
CYP3A5 genotypes in consideration, it was found that the C/D in patients with
VDR ApaI rs7975232 AA genotype was significantly lower than those with AC and CC genotypes for
CYP3A5 non-expresser(
P<0.05). However,
VDR ApaI rs7975232 gene polymorphism had no influence on C and C/D of tacrolimus in
CYP3A5 expresser. Besides, no matter in
CYP3A5 expresser or in non-expresser,
VDR BsmI rs1544410,
VDR TaqI rs731236 and
VDR FokI rs2228570 had no effect on C, D and C/D of tacrolimus.
CONCLUSION During the early stage of renal transplantation, the polymorphism of
VDR ApaI rs7975232 show significant relevance with tacrolimus concentration in
CYP3A5 non-expresser. The detection of the genotype might be helpful to guide individual therapy.