title: A common variant in the peroxisome proliferator-activated receptor-γ coactivator-1α gene is associated with nonalcoholic fatty liver disease in obese children.
abstract: BACKGROUND
  The single nucleotide polymorphism in the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α gene (PPARGC1A) was identified to be associated with nonalcoholic fatty liver disease (NAFLD) in adults. The PPARGC1A gene encodes PGC-1α, which regulates cellular energy metabolism.
  
  
  OBJECTIVE
  We aimed to test the hypothesis that the PPARGC1A rs8192678 risk A allele would influence the risk of NAFLD in obese children.
  
  
  METHODS
  We genotyped PPARGC1A rs8192678 and PNPLA3 rs738409 in 781 obese children aged 7-18 y. NAFLD was determined by ultrasonography. We evaluated the independent influence of the PPARGC1A rs8192678 risk A allele on pediatric NAFLD after control for the effect of the PNPLA3 rs738409 polymorphism.
  
  
  RESULTS
  A total of 23.3% of the recruited obese children had NAFLD. PNPLA3 rs738409 increased the OR of NAFLD by 1.622 (95% CI: 1.071, 2.457; P = 0.023) in subjects with GC alleles and 2.659 (95% CI: 1.509, 4.686; P < 0.001) for GG alleles, as compared with CC alleles. After control for the effects of age- and sex-adjusted BMI, sex, and PNPLA3 rs738409 polymorphism, the PPARGC1A rs8192678 risk A allele was an independent risk factor for developing NAFLD, with an OR of 1.740 (95% CI: 1.149, 2.637; P = 0.009). Subjects with the PPARGC1A rs8192678 risk A allele had an increase in the mean serum alanine aminotransferase concentration of 5.2 IU/L, as compared with subjects without this allele (P = 0.011).
  
  
  CONCLUSIONS
  The PPARGC1A rs8192678 risk A allele is associated with an increased risk of NAFLD, independent of the effect of the PNPLA3 rs738409 polymorphism in our population of obese Taiwanese children.
authors.affiliation: Department of Pediatrics, Far Eastern Memorial Hospital and Oriental Institute of Technology, New Taipei City, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Lin
authors.forename: Pi-Feng
authors.initials: PF
authors.lastname: Chang
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
mesh_terms: D000293:Adolescent; D000483:Alleles; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D005234:Fatty Liver / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014463:Ultrasonography; D055105:Waist Circumference; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D006360:Heat-Shock Proteins; D008049:Lipase; D008565:Membrane Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; C486497:PPARGC1A protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent