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PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery

  • Marcin Krawczyk
    Correspondence
    Correspondence: Marcin Krawczyk, M.D., Department of Medicine II, Saarland University Medical Center, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany; Jesús M. Banales, Ph.D., Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Paseo del Dr. Begiristain s/n, E-20014, San Sebastian, Spain.
    Affiliations
    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
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  • Raúl Jiménez-Agüero
    Affiliations
    Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain
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  • José M. Alustiza
    Affiliations
    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
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  • José I. Emparanza
    Affiliations
    Clinical Epidemiology Unit, CASPe, CIBER-ESP, Biodonostia Health Research Institute—HUD, San Sebastián, Spain
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  • María J. Perugorria
    Affiliations
    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
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  • Luis Bujanda
    Affiliations
    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
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  • Frank Lammert
    Affiliations
    Department of Medicine II, Saarland University Medical Center, Homburg, Germany
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  • Jesús M. Banales
    Correspondence
    Correspondence: Marcin Krawczyk, M.D., Department of Medicine II, Saarland University Medical Center, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany; Jesús M. Banales, Ph.D., Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Paseo del Dr. Begiristain s/n, E-20014, San Sebastian, Spain.
    Affiliations
    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
    Search for articles by this author

      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.

      Keywords

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