Marcin Krawczyk1, Raúl Jiménez-Agüero2, José M Alustiza3, José I Emparanza4, María J Perugorria5, Luis Bujanda6, Frank Lammert7, Jesús M Banales8. 1. 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. 2. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain. 3. 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. 4. Clinical Epidemiology Unit, CASPe, CIBER-ESP, Biodonostia Health Research Institute-HUD, San Sebastián, Spain. 5. 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. 6. 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. 7. Department of Medicine II, Saarland University Medical Center, Homburg, Germany. 8. 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.
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. OBJECTIVES: To investigate the relationship between the PNPLA3, TM6SF2, and MBOAT7 genotypes and the outcomes of bariatric surgery. SETTING: 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). CONCLUSION: 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.
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. OBJECTIVES: To investigate the relationship between the PNPLA3, TM6SF2, and MBOAT7 genotypes and the outcomes of bariatric surgery. SETTING: University hospital. METHODS: Prospectively we monitored 84 obese individuals (body mass index 35-64 kg/m2) scheduled for bariatric surgery. The PNPLA3p.I148M, TM6SF2p.E167K, and MBOAT7rs641738 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). CONCLUSION: In obesepatients, the presence of the PNPLA3p.I148M allele might be associated with greater improvement of hepatic steatosis after bariatric surgery in comparison to carriers of PNPLA3 wild-type alleles.
Authors: S Pillai; S Duvvuru; P Bhatnagar; W Foster; M Farmen; S Shankar; C Harris; E Bastyr; B Hoogwerf; A Haupt Journal: Pharmacogenomics J Date: 2017-11-21 Impact factor: 3.550
Authors: Vanda Marques; Marta B Afonso; Nina Bierig; Filipa Duarte-Ramos; Álvaro Santos-Laso; Raul Jimenez-Agüero; Emma Eizaguirre; Luis Bujanda; Maria J Pareja; Rita Luís; Adília Costa; Mariana V Machado; Cristina Alonso; Enara Arretxe; José M Alustiza; Marcin Krawczyk; Frank Lammert; Dina G Tiniakos; Bertram Flehmig; Helena Cortez-Pinto; Jesus M Banales; Rui E Castro; Andrea Normann; Cecília M P Rodrigues Journal: Front Med (Lausanne) Date: 2021-06-23