The impact of polymorphisms PNPLA3 rs738409 and TM6SF2 rs58542926 of the donor and recipient respectively on long-term patient survival after liver transplantation

Czech version

Authors: Irena Míková ¹ ; Magdaléna Neřoldová ² ; Milan Jirsa ² ; Eva Sticova ³; MUDr. Jan Mareš ⁴ ; Pavel Trunečka ¹
Published in: Gastroent Hepatol 2024; 78(4): 299-305
Category: Clinical and Experimental Gastroenterology: Review Article
doi: https://doi.org/10.48095/ccgh2024299

Overview

Introduction: The variants rs738409 c.444C>G (p.I148M) in patatin-like phospholipase domain-containing 3 (PNPLA3) and rs58542926 c.499G>A (p.E167K) in TM6SF2 (transmembrane 6 superfamily member 2) are significant genetic risk factors of development and progression of non-alcoholic fatty liver dis ease (NAFLD). In both variants, increased liver-specific mortality was described, while the impact on all-cause mortality was not proved. The aim of the study was to evaluate the impact of PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively on long-term patient survival after LT. Methods: We evaluated long-term patient survival in a cohort of 268 adult LT recipients, in whom PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively were available and steatosis was evaluated in liver graft biopsy 6–30 months after LT. The median fol low-up was 17 years. The Kaplan-Meier model was used for the survival estimates and the Cox proportional hazard model was used to assess the predictive value of the chosen variables. Results: Increased recipient age (P < 0.001), male sex (P = 0.014), alcoholic (P = 0.021) or HCV (P = 0.042) etiology of liver cirrhosis, and presence of hepatocellular carcinoma (P = 0.009) negatively influenced long-term patient survival after LT. PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the recipient and donor respectively had no effect on patient survival. Conclusion: Although PNPLA3 c.444G and TM6SF2 c.499A variants of the donor increase the risk of steatosis of the liver graft after LT, we did not prove a negative impact of these genotypes of the donor and recipient on long-term patient survival after LT.

Keywords:

PNPLA3 – TM6SF2 – steatosis – MASLD – NAFLD – liver transplantation – patient survival

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ORCID autorů

I. Míková 0000-0001-7928-7558,

M. Neřoldová 0000-0002-3792-9564,

M. Jirsa 0000-0001-7300-6735,

J. Mareš 0000-0002-4727-3685,

P. Trunečka 0000-0002-4753-4419.

Doručeno/Submitted: 28. 7. 2024

Přijato/Accepted: 1. 8. 2024

Korespondenční autorka

MUDr. Mgr. Irena Míková

Klinika hepatogastroenterologie

Institut klinické a experimentální medicíny