title: Genetic variation in the peroxisome proliferator activated receptor-gamma gene is associated with histologically advanced NAFLD.
abstract: BACKGROUND
  The peroxisome proliferator activated receptor-gamma (PPARG) is a nuclear receptor that regulates adipocyte differentiation, insulin sensitivity and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic fatty liver disease (NAFLD).
  
  
  OBJECTIVE
  We investigated the association of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological features. DNA was extracted from 274 archived, formalin-fixed liver biopsy specimens from 212 patients with NAFLD and 62 controls with normal liver histology.
  
  
  RESULTS
  Individual SNPs did not show significant association with NAFLD or its histological features. A haplotype comprised of both minor alleles (GT) was less enriched whereas a haplotype comprised of the two major alleles (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs. 28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly associated with steatosis and fibrosis. The GT haplotype was also associated with lobular inflammation.
  
  
  CONCLUSIONS
  Genetic variation in PPARG is associated with NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes that denote histologically advanced NAFLD.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53212, USA. sgawrieh@mcw.edu
authors.forename: Samer
authors.initials: S
authors.lastname: Gawrieh
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Marion
authors.forename: Richard
authors.initials: R
authors.lastname: Komorowski
authors.forename: James
authors.initials: J
authors.lastname: Wallace
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kissebah
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Michael
authors.initials: M
authors.lastname: Olivier
mesh_terms: D000328:Adult; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D047495:PPAR gamma