title: PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery.
abstract: BACKGROUND
  Obesity is the major trigger of nonalcoholic fatty liver disease (NAFLD). NAFLD is further favored by the patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M, transmembrane 6 superfamily member 2 (TM6SF2) p.E167K, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 variants.
  
  
  OBJECTIVE
  To investigate the relationship between the PNPLA3, TM6SF2, and MBOAT7 genotypes and the outcomes of bariatric surgery.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Prospectively we monitored 84 obese individuals (body mass index 35-64 kg/m2) scheduled for bariatric surgery. The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants were genotyped using restriction fragment length polymorphism analysis and TaqMan assays. Hepatic steatosis was determined before surgery using analysis of liver biopsy samples and a novel magnetic resonance imaging-based equation. One year later, steatosis was reevaluated by magnetic resonance imaging.
  
  
  RESULTS
  The presence of the PNPLA3 allle [M] was associated with increased hepatic triglyceride content (P = .03), steatosis detected by magnetic resonance imaging (P = 0.04), and decreased serum glucose concentrations (P = .04). Neither variant TM6SF2 nor MBOAT7 increased hepatic steatosis (all P>.05); however, the MBOAT7 polymorphism was associated with increased triglyceride, total cholesterol, low density lipoprotein, and serum glucose levels (all P<.05). Patients carrying the prosteatotic PNPLA3 allele [M] lost more weight (P<.01) and liver fat (P = .04) one year after surgery, as compared to individuals having the common genotype. The PNPLA3 genotype and initial grade of steatosis, but not the TM6SF2 or MBOAT7 variants, were independent predictors of NAFLD improvement (P = .03 and P<.01, respectively).
  
  
  CONCLUSIONS
  In obese patients, the presence of the PNPLA3 p.I148M allele might be associated with greater improvement of hepatic steatosis after bariatric surgery in comparison to carriers of PNPLA3 wild-type alleles.
authors: Department of Medicine II, Saarland University Medical Center, Homburg, Germany; Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. Electronic address: marcin.krawczyk@uks.eu.
authors: Marcin
authors: M
authors: Krawczyk
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain.
authors: Raúl
authors: R
authors: Jiménez-Agüero
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain; Osatek SA, San Sebastián, Spain.
authors: José M
authors: JM
authors: Alustiza
authors: Clinical Epidemiology Unit, CASPe, CIBER-ESP, Biodonostia Health Research Institute-HUD, San Sebastián, Spain.
authors: José I
authors: JI
authors: Emparanza
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
authors: María J
authors: MJ
authors: Perugorria
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
authors: Luis
authors: L
authors: Bujanda
authors: Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
authors: Frank
authors: F
authors: Lammert
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain. Electronic address: jesus.banales@biodonostia.org.
authors: Jesús M
authors: JM
authors: Banales
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000704:Analysis of Variance; D050110:Bariatric Surgery; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics*; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology; D009767:Obesity, Morbid / Q000235:genetics* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011182:Postoperative Care; D015431:Weight Loss / Q000502:physiology; D055815:Young Adult; 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: Adiponutrin; Bariatric surgery; Hepatic steatosis; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obesity; Weight loss