Effect of PNPLA3 I148M Polymorphism on Histologically Proven Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients

Abstract

Aim: PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and the best known polymorphism for nonalcoholic fatty liver disease (NAFLD). However, little is known about the effect of this polymorphism on NAFLD after liver transplantation (LT). We aimed to evaluate the association between this polymorphism and post-LT NAFLD. Methods: We designed a prospective case-control study. Among adult recipients who underwent LT between April 2014 and October 2015, those whose whole blood were preoperatively collected for genotyping in both recipients and coupled donors and those who have undergone protocol biopsy at post-LT 1 year were enrolled. Results: A total of 32 recipients were finally enrolled. Histologically proven steatosis (≥5%) were present in 28.1% of patients at a mean time of 12.7±2.0 months after LT. Moderate and more steatosis (≥33%) was present in 9.4%. One year after LT, steatosis was present in 50.0% of homozygous recipients with rs738409-G allele. It was present in 27.3% of heterozygous recipients with rs738409-G allele, and in 9.1% (p=0.041) of recipients with rs738409-CC. Genotype of donor was not significantly (p=0.647) associated with post-LT NAFLD. When both recipient and coupled donor showed heterogeneous or homozygous genotype of rs738409-G allele, there was significantly more post-LT NAFLD compared to that in others (47.1% vs. 6.7%

p=0.018). In uni- and multi-variate analysis, only the presence of rs738409-G risk allele in both donor and recipient was a significant risk factor for post-LT NALFD (relative risk, 26.95

p=0.048). Conclusions: PNPLA3 I148M polymorphism can significantly affects histologically proven NAFLD at post-LT 1 year.