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Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases
作者姓名:Rey JW  Noetel A  Hardt A  Canbay A  Alakus H  Zur Hausen A  Dienes HP  Drebber U  Odenthal M
基金项目:Supported by A grant of Marga and Walter Boll foundation
摘    要: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.

关 键 词:Single  nucleotide  polymorphism  Peroxisome  proliferator-activated  receptor  γ  Non-alcoholic  steatohepatitis  Alcoholic  steatohepatitis  Inflammation  Fibrosis  Hepatitis  Steatosis  Steatohepatitis
收稿时间:2010-06-18
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