Published online Sep 14, 2015. doi: 10.3748/wjg.v21.i34.10054
Peer-review started: April 7, 2015
First decision: May 18, 2015
Revised: June 3, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: September 14, 2015
De novo non-alcoholic fatty liver disease (NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148M and TM6SF2 E167K polymorphisms affected NAFLD susceptibility in the general population. However, this association was not validated in survivors after liver transplantation (LT). We performed a cross-sectional survey to investigate this relationship. A comprehensive survey, including anthropometric measurements, fasting venous blood sampling, ultrasound, and questionnaires was performed in the short-term. The clinical indications and patient’s steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers (0.33 vs 0.10 for GG vs CC + CG carriers, P = 0.018), while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism (0.19 in CC vs 0.14 in CT + TT carriers, P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novo NAFLD following a recessive model (GG vs CC + CG, OR = 14.2, 95%CI: 1.78-113, P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity (defined as body mass index > 25 kg/m2), steatosis was highly prevalent (71.4%) in PNPLA3 GG carriers with obesity. In conclusion, PNPLA3 I148M, but not TM6SF2 E167K, affects de novo NAFLD occurrence with a prominent interaction with obesity. Weight control might be a meaningful method to reduce the genetic susceptibility to NAFLD exerted by PNPLA3 variants.
Core tip: Previous genomic studies identified PNPLA3 I148M and TM6SF2 E167K polymorphisms as the most prominent genetic variations associated with non-alcoholic fatty liver disease (NAFLD) susceptibility in general populations. However, these impacts have never been evaluated in long-term liver transplant recipients. In a collection of survivors 10 years after liver transplantation, we found that the PNPLA3 I148M, but not TM6SF2 E167K polymorphism, affected de novo NAFLD predisposition and interacted with obesity. Our results revealed that liver transplant recipients might benefit from weight control to limit the deleterious effect exerted by genetic factors.