Impact of the <i>CYP3A5</i>, <i>CYP3A4</i>, <i>COMT</i>, <i>IL-10</i> and <i>POR</i> Genetic Polymorphisms on Tacrolimus Metabolism in Chinese Renal Transplant Recipients

<div><p>Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of <i>CYP3A5</i>, <i>CYP3A4</i>, <i>COMT</i>, <i>IL-10</i> and <i>POR</i> were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1–3, days 6–8 and days 12–14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal–Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (<i>C</i>₀/<i>D</i>) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target <i>C</i>₀ range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of <i>C</i>₀/<i>D</i> with CY<i>P3A5*3</i>, <i>CYP3A4*1G</i> and <i>CYP3A4</i> rs4646437 T>C at different time points after transplantation. The proportion of patients in the <i>IL-10 rs1800871-TT</i> group who achieved the target <i>C</i>₀ range was greater (<i>p</i> = 0.004) compared to the <i>IL-10 rs1800871-CT</i> and <i>IL-10 rs1800871-CC</i> groups at week 3 after transplantation. <i>CYP3A5*3</i>, <i>CYP3A4 *1G</i>, <i>CYP3A4</i> rs4646437 T>C and <i>IL-10</i> rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients.</p>