title: PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients.
  
  
  METHODS
  This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy.
  
  
  RESULTS
  One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group.
  
  
  CONCLUSIONS
  Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Shen
authors.forename: Grace Lai-Hung
authors.initials: GL
authors.lastname: Wong
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.forename: Ruth Suk-Mei
authors.initials: RS
authors.lastname: Chan
authors.forename: Hoi-Yun
authors.initials: HY
authors.lastname: Chan
authors.forename: Winnie Chiu-Wing
authors.initials: WC
authors.lastname: Chu
authors.forename: Bernice Ho-Ki
authors.initials: BH
authors.lastname: Cheung
authors.forename: David Ka-Wai
authors.initials: DK
authors.lastname: Yeung
authors.forename: Liz Sin
authors.initials: LS
authors.lastname: Li
authors.forename: Mandy Man-Mei
authors.initials: MM
authors.lastname: Sea
authors.forename: Jean
authors.initials: J
authors.lastname: Woo
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D008019:Life Style; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: magnetic resonance spectroscopy; non-alcoholic steatohepatitis; obesity; transient elastography; weight loss