title: Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, particularly among Hispanic Americans. A genetic variant in PNPLA3 (rs738409) has been identified as a strong predictor of hepatic fat content.
  
  
  OBJECTIVE
  To confirm the association of this variant with NAFLD in two minority cohorts, Hispanic Americans and African Americans, in whom liver density was quantified by computed tomography (CT).
  
  
  METHODS
  This analysis was conducted in the Insulin Resistance Atherosclerosis (IRAS) Family Study. Participants were recruited from the general community and included 843 Hispanic American and 371 African American adults aged 18-81 years. A single variant in PNPLA3 (rs738409) was genotyped. Liver density was calculated in Hounsfield Units from abdominal CT scans.
  
  
  RESULTS
  Single nucleotide polymorphism (SNP) rs738409 was strongly associated with reduced liver density (i.e. NAFLD) in Hispanic Americans (1.18 × 10⁻⁹) and in African Americans (P=4.99 × 10⁻⁶). The association followed an additive genetic model with the G allele conferring risk. The allele was two times more common in Hispanic Americans than in African Americans (40 vs 19%), consistent with the greater prevalence of NAFLD in Hispanic Americans (24 vs 9%). The SNP explained 4.4 and 5.6% of the variance of the adjusted liver density outcome in Hispanic Americans and African Americans, respectively.
  
  
  CONCLUSIONS
  We confirmed the association of a PNPLA3 variant with NAFLD in Hispanic Americans and African Americans, suggesting that PNPLA3 contributes to the variation in NAFLD across multiple ethnicities. This study adds to the growing evidence that some of the ethnic variation in NAFLD is genetic.
authors.affiliation: Division of Public Health Sciences, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA. lwgnkcht@wfubmc.edu
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Julie
authors.initials: J
authors.lastname: Ziegler
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Steven
authors.initials: S
authors.lastname: Haffner
authors.forename: Ann
authors.initials: A
authors.lastname: Scherzinger
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005234:Fatty Liver / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D020641:Polymorphism, Single Nucleotide; 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