Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.
BACKGROUND
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.


OBJECTIVE
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.


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.
Sharma
Sunita
S
Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA. ssharma4@partners.org
Raby
Benjamin A
BA
Hunninghake
Gary M
GM
Soto-Quirós
Manuel
M
Avila
Lydiana
L
Murphy
Amy J
AJ
Lasky-Su
Jessica
J
Klanderman
Barbara J
BJ
Sylvia
Jody S
JS
Weiss
Scott T
ST
Celedón
Juan C
JC
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000483:Alleles; D000485:Allergens / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics; D002648:Child; D004311:Double-Blind Method; D004781:Environmental Exposure; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D017835:Nedocromil / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D039981:Pyroglyphidae / Q000276:immunology*; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D000485:Allergens; D018927:Anti-Asthmatic Agents; D053773:Transforming Growth Factor beta1; D017835:Nedocromil