title: Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases.
abstract: OBJECTIVE
  To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).
  
  
  METHODS
  DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n = 263) and AFLD (n = 100) were analyzed by Real-time polymerase chain reaction using allele-specific probes.
  
  
  RESULTS
  In the NAFLD and the AFLD collective, 3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele, differing from only 1.5% cases in the healthy population. In NAFLD patients, a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease. However, we observed a significantly higher risk (odds ratio = 2.50, CI: 1.05-5.90, P = 0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations. The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD.
  
  
  CONCLUSIONS
  In AFLD patients, the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.
authors.affiliation: Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Johannes-W
authors.initials: JW
authors.lastname: Rey
authors.forename: Andrea
authors.initials: A
authors.lastname: Noetel
authors.forename: Aline
authors.initials: A
authors.lastname: Hardt
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
authors.forename: Hakan
authors.initials: H
authors.lastname: Alakus
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Dienes
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
mesh_terms: D000409:Alanine / Q000235:genetics; D001706:Biopsy; D005234:Fatty Liver / Q000235:genetics*; D006801:Humans; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics
chemical_list: D047495:PPAR gamma; D011392:Proline; D000409:Alanine