PPARG Locus Haplotype Variation and Exacerbations in Asthma

The peroxisome proliferator‐activated receptor gamma (PPARγ) 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. Clinical Pharmacology & Therapeutics (2007) 81, 713–718. doi:10.1038/sj.clpt.6100119; published online 28 February 2007.