Peroxisome proliferator-activated receptor-γ gene polymorphisms and Crohn’s disease

Abstract

Dear Editor: Recently, Sugawara et al. identified peroxisome proliferator-activated receptor-γ (PPARG) as a susceptibility gene for Crohn’s disease (CD) [Sugawara et al. (2005) Linkage to peroxisome proliferator-activated receptor-gamma in SAMP1/YitFc mice and in human Crohn’s disease. Gastroenterology 128:351–60]. PPAR-γ is a transcription factor belonging to the nuclear receptor superfamily. It initiates transcription of genes involved in diverse biological processes and inhibits the nuclear factor kappa B (NF-κB) signalling pathway. PPARG contains three promoters that yield the four mRNA isoforms PPARγ1, PPARγ2, PPARγ3, and PPARγ4 encoding two proteins. Sugawara et al. reported that two minor alleles of PPARG, namely, SNP1 [G12350898A (rs2067819)] and SNP2 [G12359887A (rs3892175)], were more common in control subjects than in CD patients. We examined the association between PPARG and CD in New Zealand by genotyping G12350898A (rs2067819), the polymorphism Pro12Ala (C34G) (rs1805192) in PPARγ2 and the PPARγ3 promoter polymorphism C681G (position −595 from ATG in exon B). A total of 182 Caucasian CD patients and 188 ethnicallymatched control subjects were genotyped by PCR-RFLP analysis using NlaIII for C681G, BsaAI for G12350898A, and BstUI for Pro12Ala. Statistical analysis was performed using the Chi-square or Fisher’s exact test. Haplotype frequencies were estimated using SHEsis (http://202.120.7.14/analysis/my Analysis.php). Linkage disequilibrium was estimated using Arlequin Ver. 2.000 (http://anthro.unige.ch/ arlequin). Genotype frequencies were analysed by the Hardy–Weinberg equilibrium (HWE) program (Institute of Human Genetics, Technical University Munich, Munich, Germany; URL: (http://ihg.gsf.de/ cgi-bin//hw/hwa1.pl)), using the Fisher’s exact test to estimate P-values. There was no significant difference in the genotype frequencies of the CD patients vs control subjects for PPARγ C681G [GG 0.632 (n=115) vs 0.590 (n=111), GA 0.308 (n=56) vs 0.346 (n=65), AA 0.060 (n=11) vs 0.064 (n=12)], PPARγ G12350898A [CC 0.681 (n=124) vs 0.649 (n=122), CG 0.264 (n=48) vs 0.293 (n=55), GG 0.055 (n=10) vs 0.058 (n=11)], and PPARγ Pro12Ala [CC 0.775 (n=141) vs 0.777 (n=146), CG 0.209 (n=38) vs 0.213 (n=40), GG 0.017 (n=3) vs 0.011 (n=2)], respectively. There was no evidence that any of the genotype distributions deviate from the Hardy– Weinberg equilibrium. There was no significant difference in the allele E. Leung . J. Hong . P. Vishnu . G. W. Krissansen (*) Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand e-mail: gw.krissansen@auckland.ac.nz Tel.: +64-9-3737599 Fax: +64-9-3737674