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Digestive Diseases and Sciences

, Volume 57, Issue 4, pp 952–957 | Cite as

Genetic Variation in the Peroxisome Proliferator Activated Receptor-Gamma Gene Is Associated with Histologically Advanced NAFLD

  • Samer Gawrieh
  • Miranda C. Marion
  • Richard Komorowski
  • James Wallace
  • Michael Charlton
  • Ahmed Kissebah
  • Carl D. Langefeld
  • Michael Olivier
Original Article

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).

Purpose and Method

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.

Keywords

PPAR gamma Gene NAFLD NASH SNP Polymorphism 

Notes

Conflict of interest

The authors have no financial relationship to disclose and no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Samer Gawrieh
    • 1
    • 2
  • Miranda C. Marion
    • 3
  • Richard Komorowski
    • 4
  • James Wallace
    • 5
  • Michael Charlton
    • 6
  • Ahmed Kissebah
    • 7
    • 8
  • Carl D. Langefeld
    • 3
  • Michael Olivier
    • 8
    • 9
    • 10
  1. 1.Division of Gastroenterology and Hepatology, Department of MedicineMedical College of WisconsinMilwaukeeUSA
  2. 2.Zablocki VA Medical CenterMilwaukeeUSA
  3. 3.Division of Public Health Sciences, Department of Biostatistical SciencesWake Forest University Health SciencesWinston-SalemUSA
  4. 4.Department of PathologyMedical College of WisconsinMilwaukeeUSA
  5. 5.Department of SurgeryMedical College of WisconsinMilwaukeeUSA
  6. 6.Department of Gastroenterology and HepatologyMayo ClinicRochesterUSA
  7. 7.Division of Endocrinology, Department of MedicineMedical College of WisconsinMilwaukeeUSA
  8. 8.Human and Molecular Genetics CenterMedical College of WisconsinMilwaukeeUSA
  9. 9.Biotechnology and Bioengineering CenterMedical College of WisconsinMilwaukeeUSA
  10. 10.Department of PhysiologyMedical College of WisconsinMilwaukeeUSA

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