title: PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity.
abstract: BACKGROUND
  Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity.
  
  
  OBJECTIVE
  The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele.
  
  
  METHODS
  PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC.
  
  
  RESULTS
  The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04).
  
  
  CONCLUSIONS
  We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD;
authors.forename: Alison
authors.initials: A
authors.lastname: Mondul
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden;
authors.forename: Rosellina M
authors.initials: RM
authors.lastname: Mancina
authors.affiliation: Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Merlo
authors.affiliation: Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.affiliation: Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;
authors.forename: Raffaela
authors.initials: R
authors.lastname: Rametta
authors.affiliation: Department of Medical and Surgical Sciences, Clinical Nutrition Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy; and.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montalcini
authors.affiliation: Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD;
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Medical and Surgical Sciences, Clinical Nutrition Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy; and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden stefano.romeo@wlab.gu.se.
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
mesh_terms: D000368:Aged; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000235:genetics*; D050177:Overweight / Q000097:blood / Q000235:genetics*; D014801:Vitamin A / Q000097:blood*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; D014801:Vitamin A; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: NAFLD; PNPLA3; RBP4; obesity; retinol