Variants in TGFB1, dust mite exposure, and disease severity in children with asthma. American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] Journal article | | Title | Variants in TGFB1, dust mite exposure, and disease severity in children with asthma. | | Author(s) | Sharma S, Raby BA, Hunninghake GM, Soto-Quirós M, Avila L, Murphy AJ, Lasky-Su J, Klanderman BJ, Sylvia JS, Weiss ST, Celedón JC | | Institution | Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA. ssharma4@partners.org | | Source | Am J Respir Crit Care Med 2009 Mar 1; 179(5):356-62. | | MeSH | Adolescent
Adrenal Cortex Hormones
Alleles
Allergens
Animals
Anti-Asthmatic Agents
Asthma
Bronchial Hyperreactivity
Child
Double-Blind Method
Environmental Exposure
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Male
Nedocromil
Polymorphism, Single Nucleotide
Pyroglyphidae
Severity of Illness Index
Transforming Growth Factor beta1
| | 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 <or= 0.01). Dust mite exposure modified the effect of the C allele of exonic SNP rs1800471 on airway responsiveness (P = 0.03 for interactions in both cohorts). The T allele of a coding SNP (rs1982073) was associated with a reduced risk of asthma exacerbations in Costa Rica (P = 0.009) and CAMP (P = 0.005). Dust mite exposure also significantly modified the effect of the A allele of the promoter SNP rs2241712 on asthma exacerbations in both cohorts.
CONCLUSIONS: SNPs in TGFB1 are associated with airway responsiveness and disease exacerbations in children with asthma. Moreover, dust mite exposure may modify the effect of TGFB1 SNPs on airway responsiveness and asthma exacerbations. | | Language | eng | | Pub Type(s) | Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
| | PubMed ID | 19096005 |
|
|
| |
Advertise on this site.
| | |
|
