BACKGROUND & AIMS: The rs738409 c.444C > G (p.I148M) polymorphism in PNPLA3 is a major factor predisposing to non-alcoholic fatty liver disease. The aim of the study was to clarify the impact of liver and extrahepatic expression of the PNPLA3 p.148M variant on liver graft steatosis after liver transplantation. METHODS: Fat content was assessed in liver biopsies from 176 transplant recipients. During a period of 4 ± 1 years after transplantation, 17 patients developed grade 3 steatosis, 14 patients grade 2 steatosis, 56 patients grade 1 steatosis, and 89 patients grade 0 steatosis. The influence of the recipient and donor rs738409 genotype and clinical and laboratory data on liver fat content were analyzed using ordinal logistic regression. RESULTS: The PNPLA3 rs738409 CC/CG/GG genotype frequencies, respectively, were 0.494/0.449/0.057 in the graft donors and 0.545/0.330/0.125 in the graft recipients. In the multivariate analysis, the presence of the PNPLA3 c.444G allele in donor (OR 1.62; 95%CI 1.12-2.33), post-transplant BMI (OR 1.14; 95%CI 1.07-1.22), diabetes mellitus (OR 1.99; 95%CI 1.22-3.22), and serum triglycerides (OR 1.40; 95%CI 1.11-1.76) were independent risk factors for increased liver graft fat content. CONCLUSIONS: These data indicate that the liver expression of the PNPLA3 p.148M variant confers a genetic predisposition to liver graft steatosis along with nutritional status and diabetes.

Center for Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Clinical and Transplant Immunology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Clinical and Transplant Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Prague Czech Republic

Medical Statistics Unit Institute for Clinical and Experimental Medicine Prague Czech Republic

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$a 10.1016/j.dld.2017.12.030 $2 doi

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$a Trunečka, Pavel $u Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: patr@ikem.cz.

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$a Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study / $c P. Trunečka, I. Míková, D. Dlouhá, JA. Hubáček, E. Honsová, L. Kolesár, V. Lánská, S. Fraňková, J. Šperl, M. Jirsa, R. Poledne,

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$a BACKGROUND & AIMS: The rs738409 c.444C > G (p.I148M) polymorphism in PNPLA3 is a major factor predisposing to non-alcoholic fatty liver disease. The aim of the study was to clarify the impact of liver and extrahepatic expression of the PNPLA3 p.148M variant on liver graft steatosis after liver transplantation. METHODS: Fat content was assessed in liver biopsies from 176 transplant recipients. During a period of 4 ± 1 years after transplantation, 17 patients developed grade 3 steatosis, 14 patients grade 2 steatosis, 56 patients grade 1 steatosis, and 89 patients grade 0 steatosis. The influence of the recipient and donor rs738409 genotype and clinical and laboratory data on liver fat content were analyzed using ordinal logistic regression. RESULTS: The PNPLA3 rs738409 CC/CG/GG genotype frequencies, respectively, were 0.494/0.449/0.057 in the graft donors and 0.545/0.330/0.125 in the graft recipients. In the multivariate analysis, the presence of the PNPLA3 c.444G allele in donor (OR 1.62; 95%CI 1.12-2.33), post-transplant BMI (OR 1.14; 95%CI 1.07-1.22), diabetes mellitus (OR 1.99; 95%CI 1.22-3.22), and serum triglycerides (OR 1.40; 95%CI 1.11-1.76) were independent risk factors for increased liver graft fat content. CONCLUSIONS: These data indicate that the liver expression of the PNPLA3 p.148M variant confers a genetic predisposition to liver graft steatosis along with nutritional status and diabetes.

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$a Míková, Irena $u Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Dlouhá, Dana $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Hubáček, Jaroslav A $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Honsová, Eva $u Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Kolesár, Libor $u Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Lánská, Věra $u Medical Statistics Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Fraňková, Soňa $u Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Šperl, Jan $u Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Jirsa, Milan $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$a Poledne, Rudolf $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

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$w MED00166709 $t Digestive and liver disease official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver $x 1878-3562 $g Roč. 50, č. 5 (2018), s. 490-495

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