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ABSTRACT
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype–gene expression associations were also assessed. Peripheral blood samples were used for genotyping of 24 SNPs on the following genes: CYP3A4, CYP3A5, CYP2E1, POR, UGT2B7, UGT1A9, ABCB1, ABCC2, ABCG2, SLCO1B1, TNF, IL2, IRF5, TGFB1, NFKBIA, IL10, IL23R, NFAT, and CCR5 by real-time PCR. The analysis of gene expression was performed by RT-qPCR. The association between graft rejection episodes and polymorphic variants was assessed using odds ratios. Polymorphisms rs7662029 (UGT2B7) and rs6714486 (UGT1A9) were associated with occurrence of graft rejection episodes, rs7662029 (UGT2B7) exhibited a protective effect (1.85-fold), and rs6714486 (UGT1A9) an increased 1.6-fold increased risk of graft rejection. Among drug transporter genes, only rs2231142 (ABCG2) demonstrated an association with a 1.92-fold decrease in the risk of graft rejection. The immunological SNP rs10889677 (IL23R) was associated with a 1.9-fold enhanced risk of graft rejection. Association between genotypes and gene expression was not detected. Therefore, SNPs of UGT2B7, UGT1A9, ABCG2, and IL23R genes may be useful as candidate markers for screening of risk graft rejection in renal transplant patients. These markers may improve medical decisions, avoiding adverse effects.
Acknowledgments
The authors thank the Kidney Institute of Londrina for support and partnership and the transplant patients that participated in the study. The authors are grateful for the assistance given by Ms. Sandra Lopes and Ms. Madalena Pikina (Clinilab, Londrina, Brazil).
Declaration of interest
The authors declare no conflicts of interest.
Funding
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 470398/2014-0] and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROAP). H.L. Cilião received scholarship of the Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná. I.M.S. Cólus and S. R. Rogatto received investigator fellowship awards from CNPq.