BACKGROUND & AIMS: The G-allele in position rs738409 of patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with an increased hepatic concentration of triglyceride and is a risk factor for advanced liver disease. We investigated the association of donor and recipient risk alleles with the development of graft steatosis after liver transplantation. METHODS: PNPLA3 genotypes were determined in 237 transplant recipients and in 255 organ donors. Macrovesicular steatosis was assessed by unenhanced computed tomography 5 years after liver transplantation in 95 patients and correlated with donor and recipient PNPLA3 genotype. RESULTS: The risk allele was significantly more frequent in transplant recipients than in donors (42% vs 28%; P < .001). A prevalence of graft steatosis of 30% or greater significantly increased from 11.6% at 1 year after liver transplantation to 32.6% at 5 years after transplantation. Five years after liver transplantation, steatosis was present in 63.2% of patients homozygous for the rs738409-G allele, in 31.4% of heterozygous recipients, and in 12.0% of rs738409-CC recipients (P = .002). Donor genotypes were not associated with the development of graft steatosis. In multivariate regression analysis, recipients who carried rs738409-GG had a 13.7-fold higher risk of graft steatosis than recipients who carried rs738409-CC (P = .022), independent of recipient age, weight gain after liver transplantation, or the underlying disease. CONCLUSIONS: Liver transplant recipients who carry rs738409-G in PNPLA3 are at increased risk for hepatic triglyceride accumulation, independent of the graft PNPLA3 genotype.
BACKGROUND & AIMS: The G-allele in position rs738409 of patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with an increased hepatic concentration of triglyceride and is a risk factor for advanced liver disease. We investigated the association of donor and recipient risk alleles with the development of graft steatosis after liver transplantation. METHODS:PNPLA3 genotypes were determined in 237 transplant recipients and in 255 organ donors. Macrovesicular steatosis was assessed by unenhanced computed tomography 5 years after liver transplantation in 95 patients and correlated with donor and recipient PNPLA3 genotype. RESULTS: The risk allele was significantly more frequent in transplant recipients than in donors (42% vs 28%; P < .001). A prevalence of graft steatosis of 30% or greater significantly increased from 11.6% at 1 year after liver transplantation to 32.6% at 5 years after transplantation. Five years after liver transplantation, steatosis was present in 63.2% of patients homozygous for the rs738409-G allele, in 31.4% of heterozygous recipients, and in 12.0% of rs738409-CC recipients (P = .002). Donor genotypes were not associated with the development of graft steatosis. In multivariate regression analysis, recipients who carried rs738409-GG had a 13.7-fold higher risk of graft steatosis than recipients who carried rs738409-CC (P = .022), independent of recipient age, weight gain after liver transplantation, or the underlying disease. CONCLUSIONS: Liver transplant recipients who carry rs738409-G in PNPLA3 are at increased risk for hepatic triglyceride accumulation, independent of the graft PNPLA3 genotype.
Authors: Michael O Baclig; Jingky P Lozano-Kühne; Cynthia A Mapua; Juliet Gopez-Cervantes; Filipinas F Natividad Journal: Int J Clin Exp Med Date: 2014-08-15