Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma
Received 16 September 2008; accepted 15 January 2009. published online 17 February 2009.
Summary
Background
The peroxisome proliferator-activated receptors (PPAR) are the nuclear hormone receptor superfamily of ligand-activated transcriptional factors. PPAR-gamma (PPARG) activation downregulates production of Th2 type cytokines and eosinophil function. Additionally, treatment with a synthetic PPARG ligand can reduce lung inflammation and IFN-gamma, IL-4, and IL-2 production in experimental allergic asthma. In patients with asthma, PPARG gene expression is known to be associated with the airway inflammatory and remodeling responses. Thus, genetic variants of PPARG may be associated with the development of asthma.
Methods
We genotyped two single nucleotide polymorphisms on the PPARG gene, +34C>G (Pro12Ala) and +82466C>T (His449His), in Korean subjects (839 subjects with asthma and 449 normal controls).
Results
Association analysis using logistic regression analysis showed that +82466C>T and haplotypes 1(CC) and 2(CT) were associated with the development of asthma (p=0.01–0.04). The frequency of PPARG-ht2 was significantly lower in the patients with asthma compared to the normal controls in codominant and dominant models (p=0.01, pcorr=0.03 and p=0.02, pcorr=0.03, respectively). Conversely, the frequency of PPARG-ht1 was significantly higher in the patients with asthma compared to the normal controls in the codominant model [p=0.04, OR: 1.27 (1.01–1.6)]. In addition, the rare allele frequency of +82466C>T was significantly lower in patients with asthma in comparison to normal controls in the codominant model (OR: 0.78, p=0.04). Thus, polymorphism of the PPARG gene may be linked to an increased risk of asthma development.
aGenome Research Center for Allergy and Respiratory Disease, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-021, Republic of Korea
bDepartment of Genetic Epidemiology, SNP Genetics, Republic of Korea
cDepartment of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea
Corresponding author. Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-021, Republic of Korea. Tel.: +82 32 621 5105; fax: +82 32 621 5016.
Corresponding author. Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea. Tel.: +82 2 705 8615; fax: +182 2 2026 4299.
ABSTRACT