BACKGROUND: Whether the loss-of-function allele CYP3A5*3 variant is associated with significantly impaired metabolism of cyclosporine A (CsA) in transplant patients is still controversial because of the lack of prospective, large-scale clinical studies performed among diversely ethnic populations. OBJECTIVES: This meta-analysis was designed to determine whether the CYP3A5*3 variant could affect CsA blood concentrations and the rate of acute rejection in renal transplant recipients. METHODS AND RESULTS: All relevant publications were retrieved online from 1966 to March 2010, in which 14 studies were chosen, and 1821 renal transplant patients were enrolled. The results showed that there were significant differences in the CsA dose-adjusted trough concentration (C0) between the CYP3A5*3/*3 and CYP3A5*1/*1 carriers [weighted mean difference (WMD): 10.06 mug/l per mg/kg, 95% confidence interval (CI): 3.12-17.00, P=0.004] and between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: 8.32 mug/l per mg/kg, 95% CI: 3.16-13.49, P=0.002). In addition, a subgroup analysis stratified by ethnicity indicated that a significant difference in CsA dose-adjusted C0 was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers in Asian patients, but not in Caucasian patients. Moreover, a significant difference in the mean daily dose was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: -0.19 mg/kg, 95% CI: -0.31 to -0.07, P=0.002). However, the meta-analysis suggested that there was little or no association of the CYP3A5*3 variant with the acute rejection rate in renal transplant patients treated with CsA [odds ratio=0.94, 95% CI: 0.57-1.54, P=0.80]. CONCLUSION: We concluded that the CYP3A5*3 variant could be associated, to a certain extent, with increased CsA dose-adjusted C0 in blood and reduced mean daily doses, but that this genetic variant allele seemed to have little effect on the acute rejection rate in renal transplant patients taking CsA.
BACKGROUND: Whether the loss-of-function allele CYP3A5*3 variant is associated with significantly impaired metabolism of cyclosporine A (CsA) in transplant patients is still controversial because of the lack of prospective, large-scale clinical studies performed among diversely ethnic populations. OBJECTIVES: This meta-analysis was designed to determine whether the CYP3A5*3 variant could affect CsA blood concentrations and the rate of acute rejection in renal transplant recipients. METHODS AND RESULTS: All relevant publications were retrieved online from 1966 to March 2010, in which 14 studies were chosen, and 1821 renal transplant patients were enrolled. The results showed that there were significant differences in the CsA dose-adjusted trough concentration (C0) between the CYP3A5*3/*3 and CYP3A5*1/*1 carriers [weighted mean difference (WMD): 10.06 mug/l per mg/kg, 95% confidence interval (CI): 3.12-17.00, P=0.004] and between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: 8.32 mug/l per mg/kg, 95% CI: 3.16-13.49, P=0.002). In addition, a subgroup analysis stratified by ethnicity indicated that a significant difference in CsA dose-adjusted C0 was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers in Asian patients, but not in Caucasian patients. Moreover, a significant difference in the mean daily dose was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: -0.19 mg/kg, 95% CI: -0.31 to -0.07, P=0.002). However, the meta-analysis suggested that there was little or no association of the CYP3A5*3 variant with the acute rejection rate in renal transplant patients treated with CsA [odds ratio=0.94, 95% CI: 0.57-1.54, P=0.80]. CONCLUSION: We concluded that the CYP3A5*3 variant could be associated, to a certain extent, with increased CsA dose-adjusted C0 in blood and reduced mean daily doses, but that this genetic variant allele seemed to have little effect on the acute rejection rate in renal transplant patients taking CsA.
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