title: PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients.
abstract: 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/m(2)), 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.
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Liu
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Tian-Chi
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Lu
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D009765:Obesity / Q000150:complications; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Liver transplantation; Non-alcoholic fatty liver disease; PNPLA3; Recipient; TM6SF2