Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of glucose and lipid metabolism, and is predominantly expressed in the liver. We aimed to evaluate the effect of donor hepatic PPARα gene polymorphisms on the development of metabolic disorders following liver transplantation (LT).A total of 176 patients undergoing primary LT were included in this Review Board-approved study. Genomic DNA was extracted from fresh frozen donor liver tissues (biopsy specimens for pathological testing at surgery). Eight single nucleotide polymorphisms in the PPARα gene were chosen from either the HapMap CHB database or previous reports.The distribution of metabolic disorders differed significantly between the wild-type and variant genotypes of both the rs5767743 and rs5767700 loci (P < 0.05 for all). After an adjustment for other factors (body mass index and tacrolimus blood concentration), the rs5767743 genetic variant was found to be an independent protective factor (P = 0.005, odds ratio = 0.416 per C allele, 95% confidence interval  = 0.225-0.768). When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPARα and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPARα gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression.