Abstract
RATIONALE: Polymorphisms in the gene for transforming growth factor-beta1 (TGFB1) have been associated with asthma, but not with airway responsiveness or disease exacerbations in subjects with asthma. OBJECTIVES: To test for association between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma severity in childhood. METHODS: We tested for the association between nine SNPs in TGFB1 and indicators of asthma severity (lung function, airway responsiveness, and disease exacerbations) in two cohorts: 416 Costa Rican parent-child trios and 465 families of non-Hispanic white children in the Childhood Asthma Management Program (CAMP). We also tested for the interaction between these polymorphisms and exposure to dust mite allergen on asthma severity. MEASUREMENTS AND MAIN RESULTS: The A allele of promoter SNP rs2241712 was associated with increased airway responsiveness in Costa Rica (P = 0.0006) and CAMP (P = 0.005), and the C allele of an SNP in the promoter region (rs1800469) was associated with increased airway responsiveness in both cohorts (P