Effect of PNPLA3 I148M polymorphism on histologically proven non-alcoholic fatty liver disease in liver transplant recipients.

Abstract

PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and best-known polymorphism for non-alcoholic 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. We designed a prospective case-control study. Among adult recipients who underwent LT between April 2014 and October 2015, those whose whole blood was preoperatively collected for genotyping in both recipients and coupled donors and those who underwent protocol biopsy at 1year post-LT were enrolled. A total of 32 recipients were enrolled. Histologically proven steatosis (≥5%) was present in 28.1% of patients at a mean time of 12.7 ± 2.0months after LT. Moderate and more severe steatosis (≥33%) was present in 9.4%. One year after LT, steatosis was present in 50.0% of homozygous recipients with the rs738409-G allele. It was present in 27.3% of heterozygous recipients with the rs738409-G allele, and in 9.1% (P = 0.041) of recipients with rs738409-CC. The genotype of the donor was not significantly (P = 0.647) associated with post-LT NAFLD. When both recipient and coupled donor showed heterogeneous or homozygous genotype of the rs738409-G allele, there was significantly more post-LT NAFLD compared to that in others (47.1% vs. 6.7%; P = 0.018). In univariate and multivariate analyses, only the presence of the 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). PNPLA3 I148M polymorphism can significantly affect histologically proven NAFLD at 1year post-LT.