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

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 (PPAR?) is expressed in the colon and has protective effects against inflammatory processes. Our aim was to examine the association of four polymorphisms of PPAR? in a well-characterized Hungarian IBD cohort. Methods: In all, 575 Crohn's disease (CD), 103 ulcerative colitis (VC) patients, and 486 sex- and age-matched controls were examined. Four polymorphisms of PPAR gamma (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] 0.12-0.94; P = 0.03), suggesting a potential protective effect of the Ala allele. The GAGG haplotype of PPAR gamma 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 x 10(-5)), while GAGC increases the risk of UC (OR 6.70; 95% CI: 3.41-13.17; P = 3.85 x 10(-10)). Conclusions: In the present study we demonstrated a significant association between PPAR gamma polymorphisms and the development of CD and UC at single loci level and also in haplotype combinations.