Z Gastroenterol 2009; 47 - A68
DOI: 10.1055/s-0029-1224047

Analysis of peroxisome proliferator-activated receptor polymorphisms in inflammatory bowel disease

K Palatka 1, S Poliska 2, M Papp 1, A Penyige 3, P Lakatos 4, P Miheller 5, T Molnár 6, I Altorjay 1, L Nagy 2
  • 1Dept. Gastroenterology, University of Debrecen, Medical and Health Science Center
  • 2Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center
  • 3Institute of Human Genetics, University of Debrecen, Medical and Health Science Center
  • 41st Dept. Medicine, Semmelweis University, Budapest
  • 52nd Dept Medicine, Semmelweis University
  • 61st Dept Medicine, University of Szeged

Peroxisome proliferator-activated receptor gamma (PPARg), is a ligand-activated transcription factor which regulates gene expression. PPARg is highly expressed in the colon, inhibiting the NF-kB activated pathway, an anti-inflammatory effect of PPARg is observed. 5-aminosalicylic acid (5-ASA) is a PPARg ligand which can induce inflammatory genes repression.

Our goal was to characterize some of these SNPs in a cohort of Crohn's disease (CD), ulcerative colitis (UC). A Hungarian Cohort study of 629 CD and 103 UC patients and 491 controls were investigated.

We examined two PPARg SNPs: Pro12Ala (exon B) and His447His (exon 6). The Pro12Ala (rs1801282) is a non-synonymous polymorphism; in which cytosine/guanine transition causes a proline/alanine substitution. The His447His (rs3856806) is a synonymous SNP where the cytosine/thymine transition does not cause amino acid substitution.

The genomic DNA was isolated from whole blood. For the genotyping we ran TaqMan assays on ABI HT7900 QPCR instrument.

The genotype frequency, Hardy-Weinberg (H-W) equilibrium (Fisher exact test) and odds ratios (OR) with 95% confidence interval were calculated.

In the case of rs1801282, we found significant difference in the allele frequency between CD and control group (p=0.026). However we got high odds ratio (OD) value 13.9, it was not significant (CI 0.767–251.6). When we analyzed the diseased patients (CD+UC vs. control), we found association of the major allele as risk factor (OD 5.3, CI 1.005–27.005, p=0.02). Analysis of rs3856806, results did not show association to the disease.

We found the minor allele of Pro12Ala, which cause a proline alanine substitution in exonB, has protective effect in homozygote genotype.

The effect of His447His SNP, a synonymous polymorphism with cytosine (C) timine (T) transition is unknown. Our results show a slight protective effect of T allele when we compared healthy patients to diseased patients, but we did not found any significant association when separated the CD and UC group.