Impact of the CYP3A4*1G Polymorphism and its Combination with CYP3A5 Genotypes on Tacrolimus Pharmacokinetics in Renal Transplant Patients

Abstract

The CYP3A4*1/*1G polymorphism was associated with the pharmacokinetics of tacrolimus, however, its contribution to dose-adjusted pharmacokinetics was approximately twofold less than that of the CYP3A5*1/*3 polymorphism. Although its effect on CYP3A4 activity is not clear, CYP3A4*1/*1G may be a candidate for a polymorphism affecting the interindividual variability in tacrolimus pharmacokinetics among CYP3A5 expressers.

Influence of Cytochrome P450 (CYP) <i>3A4*1G</i> Polymorphism on the Pharmacokinetics of Tacrolimus, Probability of Acute Cellular Rejection, and mRNA Expression Level of CYP3A5 Rather than CYP3A4 in Living-Donor Liver Transplant Patients

“…19,[24][25][26] In the present study, CYP3A4*1G genotype showed a significant association with the C/D ratio of tacrolimus in living-donor liver transplant patients comparable with data reported in kidney transplantation. 9) We showed CYP3A4*1G genotype had no correlation with the mRNA expression level of CYP3A4 both in graft liver and native intestine. Consistent with the finding by Fukushima-Uesaka et al, 8) our results showed that the CYP3A4*1/*1 genotype was strongly linked with the CYP3A5*3/*3 genotype (93.6%).…”

“…4,5) However, a newly identified SNP in the CYP3A4 gene, CYP3A4*1G affects the pharmacokinetics of some drugs. 7,9,21,22) Although some SNPs in the CYP3A4 gene such as CYP3A4*1B and CYP3A4*22 have been reported to affect the pharmacokinetics of tacrolimus, 17,23) the frequencies of CYP3A4*1B and CYP3A4*22 have not been observed in Chinese and Japanese patients. 19,[24][25][26] In the present study, CYP3A4*1G genotype showed a significant association with the C/D ratio of tacrolimus in living-donor liver transplant patients comparable with data reported in kidney transplantation.…”

“…[3][4][5][6] Recently, a new SNP in the CYP3A4 gene, CYP3A4*1G in intron 10, has been found in human lymphoblastoid cell lines from different ethnic groups and is the most common SNP in Japanese patients. 7,8) Miura et al 9) reported that dose-adjusted area under the concentration-time curve and trough level of tacrolimus in renal transplant patients with CYP3A4*1G/*1G was lower than those in patients with CYP3A4*1/*1. However, to date, no studies on this SNP have been performed in liver transplant patients in whom the genotype of the graft liver is different from that of the recipients.…”

Pharmacogenomics and personalized medicine: a review focused on their application in the Chinese population

“…The other study [45] was conducted in South China (Shanghai), where the majority of the population is Han Chinese. These conflicting results might be attributable to linkage disequilibrium (LD) between CYP3A4*1G and CYP3A5*3 in Asian populations [47][48][49] , including Han Chinese in South China [47] .…”

Associations of ABCB1, NFKB1, CYP3A, and NR1I2 polymorphisms with cyclosporine trough concentrations in Chinese renal transplant recipients

“…CYP3A4*1G is a CYP3A4 SNP with the highest occurrence in Chinese populations, but a definitive function has not been reported. A series of studies examined the relationship between the CYP3A4*1G polymorphism and drug metabolism but resulted in inconsistent findings [32][33][34] . In agreement with our observation, CYP3A4*1G was not associated with cyclosporine concentrations in 126 renal recipients [27] ; however, Qiu et al [22] and Hu et al [35] found that it was associated with a lower CsA concentration.…”