The impact of single nucleotide polymorphism in donors and recipients on the development of graft steatohepatitis after liver transplantation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16460
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Uebayashi Elena Yukie 京都大学, 医学研究科, 特定病院助教 (40938750)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: NAFLD / NASH / ASH / Steatotic liver disease / PNPLA3 / Genetic risk score / SNPs

Outline of Final Research Achievements

This study aimed to identify the genetic risk factors from donors or recipients that contribute to post-liver transplantation (LT) steatotic liver disease (SLD), focusing on the genetic risk score (GRS) based on single nucleotide polymorphisms in SLD patients.　Genotyping of PNPLA3, TM6SF2, and HSD17B13 was performed, and the combined GRS was calculated. The relationship between the GRS and the incidence of post-transplant SLD was also evaluated. Donor risk alleles of PNPLA3, TM6SF2, and HSD17B13, rather than recipient risk alleles, have been implicated in the development of post-transplant SLD. A high donor GRS was an independent risk factor for post-LT SLD.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

脂肪性肝疾患はせっかく肝移植を行ったにも関わらず高率に再発する難治性疾患である。肝移植後の生活習慣等が再発に寄与していると指摘されてきたが、本研究は肝移植患者の遺伝的リスクアレルに着目した。本研究はレシピエントでは無く、ドナーのリスクアレル保有が肝移植後脂肪性肝疾患の発症に関与することを示した。ドナーのリスクアレルを組み合わせた遺伝的リスクスコアを用いることで肝移植後脂肪性肝疾患の発症を予測し得る可能性を示した。肝移植後脂肪性肝疾患の発症、進展を防ぐための治療計画策定に有用と思われる。