Irena Míková1, Magdaléna Neřoldová2, Jaroslav A Hubáček2, Dana Dlouhá2, Milan Jirsa2, Eva Honsová3, Eva Sticová3, Věra Lánská4, Julius Špičák1, Pavel Trunečka1. 1. Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 2. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 3. Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 4. Medical Statistics Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Abstract
BACKGROUND: The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation. METHODS: Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression. RESULTS: The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present. CONCLUSIONS: The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele.
BACKGROUND: The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donorTM6SF2rs58542926 genotypes on liver graft fat content after liver transplantation. METHODS:Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donorTM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression. RESULTS: The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donorTM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present. CONCLUSIONS: The donorTM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donorPNPLA3 c.444G allele.
Authors: Pablo Gabriel-Medina; Roser Ferrer-Costa; Francisco Rodriguez-Frias; Andreea Ciudin; Salvador Augustin; Jesus Rivera-Esteban; Juan M Pericàs; David Martinez Selva Journal: Biomedicines Date: 2022-04-28
Authors: Tomislav Kelava; Petra Turcic; Antonio Markotic; Ana Ostojic; Dino Sisl; Anna Mrzljak Journal: World J Gastroenterol Date: 2020-03-28 Impact factor: 5.742
Authors: Denisa Erhartova; Monika Cahova; Helena Dankova; Marie Heczkova; Irena Mikova; Eva Sticova; Julius Spicak; Ondrej Seda; Pavel Trunecka Journal: PLoS One Date: 2019-11-08 Impact factor: 3.240