IMPACT OF GENETIC POLYMORPHISMS AT THE PROMOTER AREA OF IL-10 GENE ON TACROLIMUS LEVEL IN JORDANIAN RENAL TRANSPLANTATION RECIPIENTS

Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable variability. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3-Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients. Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/ AA: 38, 46.7, 15.2%); IL- 10 (-819) wereCC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL- 10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation [88.2 +/- 32.1 vs. 117.5 +/- 22.5 ng/mL per mg/kg/day, p=0.04]. Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the firstmonth post-transplantation.