title: PNPLA3 genotype increases susceptibility of nonalcoholic steatohepatitis among obese patients with nonalcoholic fatty liver disease.
abstract: BACKGROUND
  The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with histologic disease severity in patients with nonalcoholic fatty liver disease (NAFLD); however, whether the PNPLA3 genotype has an effect on susceptibility of nonalcoholic steatohepatitis (NASH) from NAFLD among severely obese patients remains unclear. The objective of this study was to investigate the role of the PNPLA3 genotype on NASH in severely obese Asian patients with NAFLD.
  
  
  METHODS
  The PNPLA3 rs738409 genotype was determined in 181 severely obese patients who underwent bariatric surgery. The diagnosis of NASH and the NAFLD activity score (NAS) were determined by liver histopathology.
  
  
  RESULTS
  Of the 181 patients, 29 (16.0%), 60 (33.2%), and 92 (50.8%) were in the non-NAFLD, steatosis, and NASH groups, respectively. The PNPLA3 rs738409 GG genotype was associated with higher liver enzymes and a higher risk for NASH (odds ratio [OR], 3.72; 95% CI, 1.25-11.05). The GG genotype was also associated with histologic severity of NAFLD, including higher steatosis grade (OR, 9.94; 95% CI, 2.20-44.83 for patients with grade 3 steatosis) and NAS (OR, 11.49; 95% CI, 2.50-52.83 for patients with a NAS ≥5). Finally, multiple logistic regression also showed that the GG genotype was an independent risk factor for NASH (OR, 3.58; 95% CI, 1.15-11.12) in NAFLD patients.
  
  
  CONCLUSIONS
  The PNPLA3 rs738409 GG genotype increases susceptibility of NASH in severely obese Asians with NAFLD and correlates to histologic severity of NAFLD.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Bariatric and Metabolic International Surgery Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Tai
authors.affiliation: Bariatric and Metabolic International Surgery Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chih-Kun
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Tu
authors.affiliation: Department of Pathology, Lin Shin Hospital, Taichung, Taiwan.
authors.forename: Jau-Chung
authors.initials: JC
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Center and Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D050110:Bariatric Surgery; D001706:Biopsy; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D009767:Obesity, Morbid / Q000150:complications* / Q000601:surgery; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D004247:DNA; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Bariatric surgery; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obesity; PNPLA3