Dataset Information

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor ?2 in patients with fatty liver diseases.

ABSTRACT: AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-? (PPAR?)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 PPAR?2-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 PPAR?2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPAR?2 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.

SUBMITTER: Rey JW

PROVIDER: S-EPMC3001974 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases.

Rey Johannes-W JW Noetel Andrea A Hardt Aline A Canbay Ali A Alakus Hakan H Zur Hausen Axel A Dienes Hans-Peter HP Drebber Uta U Odenthal Margarete M

World journal of gastroenterology 20101201 46

<h4>Aim</h4>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).<h4>Methods</h4>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-speci ...[more]

PMID: 21155004

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Project description:BackgroundPeroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor, has been implicated playing a role in the development of inflammatory bowel disease (IBD). However, previous studies evaluating the association between the PPARγ2 Pro12Ala polymorphism and IBD are inconsistent. We performed a meta-analysis to determine whether the PPARγ2 Pro12Ala mutation was associated with the presence of IBD.Methods and findingsElectronic databases were searched for case-control studies evaluating the association between the Pro12Ala mutation and the presence of IBD. Effects were summarized with the methods recommended by the Cochrane Collaboration. A total of 7 studies including 1002 ulcerative colitis (UC) cases, 1090 Crohǹs disease (CD) cases and 1983 controls were involved in this meta-analysis. In the overall analysis, no significant association of this polymorphism with UC or CD was found. In the subgroup analyses in different populations, AlaAla genotype seemed to protect the European Caucasian population against the development of CD (Pro vs Ala: OR = 1.135, 95%CI = 0.951-1.354, P = 0.162, Bon = 1.000; ProPro vs ProAla: OR = 1.042, 95%CI = 0.852-1.273, P = 0.690, Bon = 1.000; ProPro vs AlaAla: OR = 2.379, 95%CI = 1.110-5.100, P = 0.026, Bon = 0.156; ProAla vs AlaAla: OR = 2.315, 95%CI = 1.064-5.037, P = 0.034, Bon = 0.204; Pro homozygotes vs Ala positives: OR = 1.094, 95%CI = 0.899-1.330, P = 0.371, Bon = 1.000; Pro positives vs Ala homozygotes: OR = 2.360, 95%CI = 1.103-5.053, P = 0.027, Bon = 0.162; heterozygotes vs all homozygotes: OR = 0.976, 95%CI = 0.799-1.192, P = 0.809, Bon = 1.000). There was no significant association of this polymorphism with UC or CD in the East Asian population and the Turkish population.ConclusionAlaAla genotype may be a protective factor in the European Caucasian population against the development of CD in a recessive way.

Project description:IntroductionPrematurity is the leading cause of death and disability in children under 5 years of age. Understanding the molecular mechanisms of the biological processes involved in preterm brain injury may help develop novel neuroprotective treatment strategies. A growing body of evidence suggest that peroxisome proliferator-activated receptor gamma (PPARγ) signaling is associated with inhibited brain development in preterm babies. The Ala allele of the Pro12Ala polymorphism of PPARγ2 decreases receptor binding affinity and consequently induces a reduction of PPARγ signaling.MethodsIn this study, we carried out a preliminary analysis of existing datasets to test the hypothesis that reduced transactivation capacity of PPARγ in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm babies. The association between PPAR-γ2 Pro12Ala polymorphism and neurodevelopment at 18-24 months of age was assessed in two groups of European infants, 155 born before 33 weeks' gestation and 180 born later than 36 weeks' gestation using a linear regression model. The Bayley Scales of Infant and Toddler Development-3rd edition was administered to assess neurodevelopment at 18-24 months of age.ResultsWe observed the Ala allele of the Pro12Ala polymorphism in 25% preterm infants and 20% term infants. The Ala allele of PPARγ2 was significantly associated with adverse cognitive (p = .019), language (p = .03), and motor development (p = 0.036) at 18-24 months of age after taking into consideration the duration of ventilation, gender, and index of multiple deprivation scores, but without correction for potential shared ancestry. There was no association between the PPAR-γ2 Pro12Ala polymorphism and neurodevelopment in term infants.ConclusionsThese preliminary data suggest that PPARγ signaling in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm infants suggesting that further studies are warranted.

Dataset Information

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor ?2 in patients with fatty liver diseases.

Publications

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases.

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