Association analysis of peroxisome proliferator-activated receptors gamma gene polymorphisms with asprin hypersensitivity in asthmatics.
- Author:
Sun Hee OH
1
;
Se Min PARK
;
Jong Sook PARK
;
An Soo JANG
;
Yong Mok LEE
;
Soo Taek UH
;
Young Hoon KIM
;
In Seon CHOI
;
Mi Kyeong KIM
;
Byeong Lae PARK
;
Hyoung Doo SHIN
;
Choon Sik PARK
Author Information
- Publication Type:Original Article
- Keywords: peroxisome proliferator-activated receptors gamma; aspirin; asthma; gene; polymorphism
- MeSH: Alleles; Aspirin; Asthma; Cytokines; Eosinophils; Haplotypes; Humans; Hypersensitivity; Inflammation; Ligands; Logistic Models; Peroxisome Proliferator-Activated Receptors; Peroxisomes; Polymorphism, Single Nucleotide; PPAR gamma
- From:Allergy, Asthma & Immunology Research 2009;1(1):30-35
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
