title: Healthy PNPLA3 risk allele carriers present with unexpected body fat composition. A study of one thousand subjects.
abstract: BACKGROUND
  The common PNPLA3 (adiponutrin) variant p.I148M represents a major genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with traits of the metabolic syndrome, therefore it is mostly suspected in obese individuals. Here, we investigate the association between the PNPLA3 variant and anthropometric traits in a cohort of healthy individuals.
  
  
  METHODS
  We recruited 1,000 (500 females; age 18-66 years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. We also determined the percentage of total fat (F%) and active tissue (TA%) of body weight.
  
  
  RESULTS
  Healthy carriers of the PNPLA3 [IM] and [MM] genotypes, although not differing in height from individuals with the genotype [II], displayed significantly lower body weight and lower BMI (both P = 0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest and shin circumferences (all P < 0.05). Separate analysis for males and females demonstrated an association between the [IM] and [MM] genotypes and higher TA% but lower F% (P = 0.04) in females. In males, BMI and total weight were significantly (P = 0.04) lower among carriers of the [M] allele.
  
  
  CONCLUSIONS
  Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner as compared to the carriers of the common allele. Hence in clinical practice they might be overlooked since they do not necessarily present with the anthropometric characteristics commonly associated with severe hepatic steatosis.
authors.affiliation: Medical Biology Laboratory Pomeranian Medical University, Szczecin, Poland. marcin.krawczyk@uks.eu.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kempinska-Podhorodecka
authors.affiliation: Department of Medicine II Saarland University Medical Center, Homburg, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Medical Biology Laboratory Pomeranian Medical University, Szczecin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Klak
authors.affiliation: Medical Biology Laboratory Pomeranian Medical University, Szczecin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Blatkiewicz
authors.affiliation: Department of Medicine II Saarland University Medical Center, Homburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.affiliation: Liver Research Laboratories Pomeranian Medical University, Szczecin, Poland;Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery.
authors.forename: Piotr
authors.initials: P
authors.lastname: Milkiewicz
authors.affiliation: Medical Biology Laboratory Pomeranian Medical University, Szczecin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Milkiewicz
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000886:Anthropometry / Q000379:methods; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000473:pathology; 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