title: Peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms in nonalcoholic fatty liver disease: a study in Brazilian patients.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis in the absence of excess alcohol consumption. The pathogenesis of fatty liver disease and steatohepatitis (NASH) is not fully elucidated, but the common association with visceral obesity, hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM) suggests that it is the hepatic manifestation of metabolic syndrome. Peroxisome proliferator-activated receptor PPARα and PPARγ are members of a family of nuclear receptors involved in the metabolism of lipids and carbohydrates, adipogenesis and sensitivity to insulin. The objective of this study was to analyze the polymorphisms Leu162Val of PPARα and Pro12Ala of PPARγ as genetic risk factors for the development and progression of NAFLD.
  
  
  METHODS
  One hundred and three NAFLD patients (89 NASH, 14 pure steatosis) and 103 healthy volunteers were included. Single nucleotide polymorphisms (SNPs) Leu162Val and Pro12Ala were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  NASH patients presented higher BMI, AST and prevalence of T2DM than patients with pure steatosis. A higher prevalence of 12Ala allele was observed in the NASH Subgroup when compared to Control Group. When we grouped NASH and Steatosis Subgroups (NAFLD), we found lower serum glucose and more advanced fibrosis in the Leu162Val SNP. On the other hand, there was no statistical difference in clinical, laboratorial and histological parameters according to the Pro12Ala SNP.
  
  
  CONCLUSIONS
  We documented a lower prevalence of 12Ala allele of gene PPARγ in the NASH Subgroup when compared to Control Group. In NAFLD patients, there were no associations among the occurrence of Pro12Ala SNP with clinical, laboratorial and histological parameters. We also documented more advanced fibrosis in the Leu162Val SNP. The obtained data suggest that Pro12Ala SNP may result in protection against liver injury and that Leu162Val SNP may be involved in the progression of NAFLD.
authors.affiliation: Clinical Nutrition Division, Department of Internal Medicine, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil; Gastroenterology Division, Department of Internal Medicine, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil; Department of Pathology and Legal Medicine, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address: ferdomenici@yahoo.com.
authors.forename: Fernanda Aparecida
authors.initials: FA
authors.lastname: Domenici
authors.forename: Maria José Franco
authors.initials: MJ
authors.lastname: Brochado
authors.forename: Ana de Lourdes Candolo
authors.initials: Ade L
authors.lastname: Martinelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Zucoloto
authors.forename: Selma Freire de Carvalho
authors.initials: SF
authors.lastname: da Cunha
authors.forename: Helio
authors.initials: H
authors.lastname: Vannucchi
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D047493:PPAR alpha / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D047493:PPAR alpha; D047495:PPAR gamma
keywords: NAFLD; NASH; Nonalcoholic fatty liver disease; PPAR; Peroxisome proliferator-activated receptor; Polymorphism; SNPs; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; single nucleotide polymorphisms