Background: Graft acceptance against immunity is one of the major challenges in solid organ transplant.
Immunosuppressive medications have effectively improved the post-transplantation outcome however, it
has its own limitations. Genetic polymorphisms in drug-metabolizing enzymes have been identified as the potential
targets in developing a pharmacogenetic strategy, to individualize drug dose and also in preventing the
Objective: The rationale of the study was to explore polymorphisms in tacrolimus and mycophenolate
metabolic pathways that influence the adverse clinical outcomes in renal transplant recipients.
Methods: A total of 255 renal transplant recipients were analyzed for the pharmacogenetic determinants of
tacrolimus (CYP3A5*3 ABCB1 1236 T>C ABCB1 2677 G>A/T ABCB1 3435 T>C) and mycophenolate
(UGT1A8*3 UGT1A9 IMPDH I IMPDH II c.787C>T ABCC2 -24 C>T and c.3972C>T) using Sanger sequencing.
Results: Acute rejection (AR) was observed in 5.88% of the transplant recipients whereas acute tubular necrosis
(ATNs) was observed in 7.45% of the patients within early stage of the maintenance phase. Infections such
as urinary tract infection (UTI) and cytomegalovirus (CMV) infection were observed in 11.37% and 12.16% of
the patients. The AUC of mycophenolate was significantly higher in patients with increased risk for infections.
ABCC2 -24 C>T c.3972C>T polymorphisms and ABCB1 3435 C-allele were associated with reduced risk for
infections. ABCC2 rs3740066 was associated with 2.06-fold all-cause mortality risk. CYP3A5 AG- and
UGT1A9-440 CC-genotypes showed increased risk and ABCC 3972C>T CC-genotype showed protection
against adverse events.
Conclusion: Genetic variants in tacrolimus and mycophenolate metabolic pathways were found to influence
the morbidity and mortality in renal transplant recipients.