PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients

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 I148 M and TM6SF2 E167 K polymorphisms affected NAFLD susceptibility in the general population. However,this association was not validated in survivors after liver transplantation(LT). We performed a crosssectional survey to investigate this relationship. A comprehensive survey,including anthropometric measurements,fasting venous blood sampling,ultrasound,and questionnaires was performed in the shortterm. 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 novoNAFLD 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 Table 1 Current status of long-term recipients surviving more than 10 years Univariate Multivariate NAFLD(n = 12)Control(n = 53)P value OR P value Age(yr) 56.5 ± 8.4 53.6 ± 10.1 0.356 1.04(0.92-1.18)0.528Gender(M/F) 10/2 47/6 0.611 1.40(0.14-14.2)0.427 Indication for LT Hepatitis/cirrhosis/ cancer/others1/8/2/17/35/9/20.889 Survival time(yr) 11.2 ± 0.9 11.5 ± 1.4 0.541 BMI(kg/m2) 25.1 ± 3.0 22.5 ± 2.6 0.003 1.47(1.03-2.08)0.032 TG(mmol/L) 1.6 ± 1.1 1.1 ± 0.6 0.038 1.34(0.38-4.71)0.652 HDL-C(mmol/L) 1.2(1.0-1.4) 1.3(1.0-1.7) 0.267 FBG(mmol/L) 7.6 ± 3.4 5.7 ± 1.9 0.013 1.49(0.93-2.37)0.095 Hypertension(Yes/no)3/9 21/32 0.343 SUA(μmol/L) 381.6 ± 75.6 342.6 ± 76.4 0.116 Met S(Yes/no) 4/8 9/44 0.201 ALT(U/L) 36.7 ± 7.0 38.8 ± 6.7 0.882 Alcohol intake(g/wk)11.6 ± 7.3 21.0 ± 8.2 0.766 Smoking(cigar/d) 4.2 ± 3.4 4.3 ± 1.2 0.969 Exercise(min/d) 18.5 ± 6.0 22.9 ± 2.9 0.513 Immunosuppression Tacrolimus/ cyclosporine/ MMF/sirolimus/ none11/1/0/0/036/12/1/2/20.575 PNPLA3(CC/CG/GG)1/3/8 16/21/16 0.018 14.2(1.78-113)0.012 TM6SF2(CC/CT/TT)11/1/0 47/5/1 0.883 2.68(0.25-28.5)0.413 Continuous v