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Association of peroxisome proliferator-activated receptor gamma polymorphisms with inflammatory bowel disease in a Hungarian cohort

Authors

  • Szilard Poliska MSc,

    1. Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary
    2. Clinical Genomics Center, Medical and Health Science Center, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary
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    • The first two authors contributed equally to the study.

  • Andras Penyige PhD,

    1. Department of Human Genetics, University of Debrecen, Debrecen, Hungary
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    • The first two authors contributed equally to the study.

  • Peter Laszlo Lakatos MD, PhD,

    1. 1st Department of Medicine, Semmelweis University, Budapest, Hungary
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  • and the Hungarian IBD Study Group,

    1. 1st Department of Medicine, Semmelweis University, Budapest, Hungary
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  • Maria Papp MD, PhD,

    1. 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
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  • Karoly Palatka MD, PhD,

    1. 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
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  • Laszlo Lakatos MD, PhD,

    1. 1st Department of Medicine, Csolnoky F. County Hospital, Veszprem, Hungary
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  • Tamas Molnar MD, PhD,

    1. 1st Department of Medicine, University of Szeged, Szeged, Hungary
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  • Laszlo Nagy MD, PhD

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary
    2. Clinical Genomics Center, Medical and Health Science Center, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary
    3. Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, Research
    • Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary
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  • Laszlo Nagy is an International Scholar of HHMI and holds a Wellcome Trust Senior Research Fellowship in Biomedical Sciences and is also supported by grants from the Hungarian Scientific Research Fund (OTKA NK72730), TAMOP-4.2.2/08/1, and TÁMOP-4.2.1/B-09/1/KONV-2010-0007. This work was also supported by grants from the National Office for Research and Technology (NKFP 1/007/01, NKFP 1A/008/04) and from the Hungarian National Research Fund (NI 67877).

Abstract

Background:

Inflammatory bowel disease (IBD) shows increasing incidence in the last few years in Eastern Europe, including Hungary. Since genetic susceptibility of patients plays an important role in the development and pathogenesis of IBD, it is important to identify new susceptibility genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in the colon and has protective effects against inflammatory processes. Our aim was to examine the association of four polymorphisms of PPARγ in a well-characterized Hungarian IBD cohort.

Methods:

In all, 575 Crohn's disease (CD), 103 ulcerative colitis (UC) patients, and 486 sex- and age-matched controls were examined. Four polymorphisms of PPARγ (rs10865710 [C-681G], rs2067819, rs3892175, and rs1801282 [Pro12Ala]) were genotyped by TaqMan genotyping assays.

Results:

The Pro12Ala polymorphism showed significant association with CD when the frequencies of the homozygous variants (Pro/Pro vs. Ala/Ala) were compared. The minor Ala/Ala genotype was significantly less frequent in CD patients compared to the controls (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 012–0.94; P = 0.03), suggesting a potential protective effect of the Ala allele. The GAGG haplotype of PPARγ confers a protective effect in CD; however, it is not significant, but in UC it has a protective effect with a significant level (OR = 0.14; 95% CI: 0.05–0.42; P = 3.78 × 10−5), while GAGC increases the risk of UC (OR = 6.70; 95% CI: 3.41–13.17; P = 3.85 × 10−10).

Conclusions:

In the present study we demonstrated a significant association between PPARγ polymorphisms and the development of CD and UC at single loci level and also in haplotype combinations. (Inflamm Bowel Dis 2012;)

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