title: Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis.
abstract: OBJECTIVE
  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.affiliation: Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Finkenstedt
authors.forename: Claudia
authors.initials: C
authors.lastname: Auer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Glodny
authors.forename: Ursula
authors.initials: U
authors.lastname: Posch
authors.forename: Hansjoerg
authors.initials: H
authors.lastname: Steitzer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lanzer
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Matthias
authors.initials: M
authors.lastname: Biebl
authors.forename: Michael
authors.initials: M
authors.lastname: Steurer
authors.forename: Ivo
authors.initials: I
authors.lastname: Graziadei
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Heinz
authors.initials: H
authors.lastname: Zoller
mesh_terms: D000328:Adult; D000368:Aged; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D014180:Transplantation; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: ALD; Alcoholic Liver Disease; BMI; CT; CT(LP); Genetics; LT; NAFLD; Nonalcoholic Fatty Liver Disease; PNPLA3; Variant; alcoholic liver disease; blood-free hepatic attenuation; body mass index; computed tomography; liver transplantation; nonalcoholic fatty liver disease; patatin-like phospholipase domain-containing protein 3