Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period.

AIM

Pharmacogenetics holds the potential to elucidate the inherited basis of differences between individual responses to drugs. Impacts of CYP3A5 and ABCB1 gene polymorphisms on the immunosuppressant tacrolimus have been reported in previous studies of liver transplantation. The functions of interleukin-10 (IL-10) gene expression are complex in the early period after liver transplantation. In this study, we examined the IL-10 genotypes of both recipients and donors to clarify the influence of these genetic variants on tacrolimus dose requirements and pharmacokinetics.

METHODS

Genetic polymorphisms of IL-10, CYP3A5, and ABCB1 were evaluated for 53 liver transplant recipients and 53 donors. Tacrolimus doses and blood concentrations were determined at 1, 2, and 3 weeks, and 1 month after transplantation. IL-10 polymorphisms at G-1082A, C-819 T, and C-592A; CYP3A5 polymorphisms at A6986G; and ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by PCR amplification and DNA sequencing.

RESULTS

Recipients who received organs from CYP3A5*3/*3 donors had higher tacrolimus C/D ratios. In the first 2 weeks, the tacrolimus C/D ratios of the recipients with donors who were CYP3A5 nonexpressors and had a low IL-10 production genotype (-819TT, -592 AA) were higher than those with donors who were CYP3A5 nonexpressors and had a high IL-10 production genotype (-819CC or CT, -592CC or AC). There were no significant differences in laboratory data or clinical characteristics (which could influence the tacrolimus C/D ratio) between the two groups of patients (P > 0.05).

CONCLUSION

Determining IL-10 and CYP3A5 polymorphisms of donors may allow individualized tacrolimus dosage regimens to be determined for liver transplant patients during the early posttransplantation period.