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PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery.
Surg Obes Relat Dis. 2016 Dec; 12(10):1838-1846.SO

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.

Authors+Show 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. Electronic address: marcin.krawczyk@uks.eu.Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital (HUD), University of the Basque Country (UPV/EHU), San Sebastián, Spain.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.Clinical Epidemiology Unit, CASPe, CIBER-ESP, Biodonostia Health Research Institute-HUD, San Sebastián, Spain.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.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.Department of Medicine II, Saarland University Medical Center, Homburg, Germany.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27576208

Citation

Krawczyk, Marcin, et al. "PNPLA3 p.I148M Variant Is Associated With Greater Reduction of Liver Fat Content After Bariatric Surgery." Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery, vol. 12, no. 10, 2016, pp. 1838-1846.
Krawczyk M, Jiménez-Agüero R, Alustiza JM, et al. PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery. Surg Obes Relat Dis. 2016;12(10):1838-1846.
Krawczyk, M., Jiménez-Agüero, R., Alustiza, J. M., Emparanza, J. I., Perugorria, M. J., Bujanda, L., Lammert, F., & Banales, J. M. (2016). PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery. Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery, 12(10), 1838-1846. https://doi.org/10.1016/j.soard.2016.06.004
Krawczyk M, et al. PNPLA3 p.I148M Variant Is Associated With Greater Reduction of Liver Fat Content After Bariatric Surgery. Surg Obes Relat Dis. 2016;12(10):1838-1846. PubMed PMID: 27576208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery. AU - Krawczyk,Marcin, AU - Jiménez-Agüero,Raúl, AU - Alustiza,José M, AU - Emparanza,José I, AU - Perugorria,María J, AU - Bujanda,Luis, AU - Lammert,Frank, AU - Banales,Jesús M, Y1 - 2016/07/01/ PY - 2016/01/11/received PY - 2016/05/30/revised PY - 2016/06/29/accepted PY - 2016/9/1/pubmed PY - 2017/8/29/medline PY - 2016/8/31/entrez KW - Adiponutrin KW - Bariatric surgery KW - Hepatic steatosis KW - Nonalcoholic fatty liver disease KW - Nonalcoholic steatohepatitis KW - Obesity KW - Weight loss SP - 1838 EP - 1846 JF - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JO - Surg Obes Relat Dis VL - 12 IS - 10 N2 - 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. SN - 1878-7533 UR - https://www.unboundmedicine.com/medline/citation/27576208/PNPLA3_p_I148M_variant_is_associated_with_greater_reduction_of_liver_fat_content_after_bariatric_surgery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1550-7289(16)30158-7 DB - PRIME DP - Unbound Medicine ER -