PPARG locus haplotype variation and exacerbations in asthma.
The peroxisome proliferator-activated receptor gamma (PPARgamma) regulates inflammation and may play a role in asthma. Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of previously characterized single-nucleotide polymorphisms in the PPARG gene (Pro12Ala, C1431T, and C-681G) with asthma exacerbations in patients aged 3-22 years (n=569). The common homozygous haplotype combination of the Pro12 and C1431 alleles was associated with increased risk for asthma exacerbations (ProC, odds ratio (OR) 1.87, 95% confidence interval 1.25-2.79; P=0.002). The ProC genotype was associated with increased school absences (OR 1.82, 95% confidence interval 1.21-2.76; P=0.004) and hospital admissions (OR 2.32, 95% confidence interval 1.18-4.58; P=0.015) over the preceding 6 months. The population-attributable risk of this genotype was 33%. Common genetic variation at the PPARG locus may play an important role in modulating the long-term control of asthma in children and young adults.
Palmer
C N A
CN
Biomedical Research Centre, Ninewells Hospital, University of Dundee, Scotland, UK.
Doney
A S F
AS
Ismail
T
T
Lee
S P
SP
Murrie
I
I
Macgregor
D F
DF
Mukhopadhyay
S
S
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D018570:Risk Assessment; D006113:United Kingdom / Q000453:epidemiology
D047495:PPAR gamma; D004247:DNA