Association analysis of peroxisome proliferator-activated receptors gamma gene polymorphisms with asprin hypersensitivity in asthmatics.
OBJECTIVE
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 FEV(1) 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.
Oh
Sun-Hee
SH
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University, Bucheon Hospital, Bucheon, Korea.
Park
Se-Min
SM
Park
Jong-Sook
JS
Jang
An-Soo
AS
Lee
Yong-Mok
YM
Uh
Soo-Taek
ST
Kim
Young Hoon
YH
Choi
In-Seon
IS
Kim
Mi-Kyeong
MK
Park
Byeong Lae
BL
Shin
Hyoung-Doo
HD
Park
Choon-Sik
CS
aspirin; asthma; gene; peroxisome proliferator-activated receptors gamma; polymorphism