Rey JW, Noetel A, Hardt A, Canbay A, Alakus H, Hausen AZ, Dienes HP, Drebber U, Odenthal M. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases. World J Gastroenterol 2010; 16(46): 5830-5837 [PMID: 21155004 DOI: 10.3748/wjg.v16.i46.5830]
Corresponding Author of This Article
Margarete Odenthal, PhD, Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Cologne, Germany. m.odenthal@uni-koeln.de
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Brief Article
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World J Gastroenterol. Dec 14, 2010; 16(46): 5830-5837 Published online Dec 14, 2010. doi: 10.3748/wjg.v16.i46.5830
Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases
Johannes W Rey, Andrea Noetel, Aline Hardt, Ali Canbay, Hakan Alakus, Axel zur Hausen, Hans Peter Dienes, Uta Drebber, Margarete Odenthal
Johannes W Rey, Andrea Noetel, Aline Hardt, Hans Peter Dienes, Uta Drebber, Margarete Odenthal, Institute for Pathology, University Hospital of Cologne, 50924 Cologne, Germany
Ali Canbay, Department of Gastroenterology and Hepatology, University Hospital of Essen, 45147 Essen, Germany
Hakan Alakus, Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, 50924 Cologne, Germany
Axel zur Hausen, Institute for Pathology, University Hospital of Freiburg, 79104 Freiburg/Brisgau, Germany
Author contributions: Rey JW and Noetel A are equally contributed to the work; Rey JW and Noetel A performed the laboratory research and analyzed the data; Canbay A contributed to final review of the manuscript and critical discussion; zur Hausen A performed DNA isolation of the blood samples; Alakus H helped with the statistical analysis; Hardt A, Drebber U and Dienes HP were responsible for scoring; Odenthal M designed the study; Odenthal M and Noetel A wrote the manuscript.
Supported by A grant of Marga and Walter Boll foundation
Correspondence to: Margarete Odenthal, PhD, Institute for Pathology, University Hospital Cologne, Kerpener Str. 62, 50924 Cologne, Germany. m.odenthal@uni-koeln.de
Telephone: +49-221-4786367 Fax: +49-221-4786360
Received: June 18, 2010 Revised: July 27, 2010 Accepted: August 3, 2010 Published online: December 14, 2010
Abstract
AIM: 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.
CONCLUSION: 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.
