期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 179, 期 5, 页码 356-362出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200808-1268OC
关键词
airway responsiveness; asthma; dust mite allergen; single nucleotide polymorphisms; transforming growth factor-beta 1
资金
- NIH [HL04370, HL66289, U01 HL075419, U01 HL65899, POI HL083069, R01 HL086601, N01HRl 6049, T32 HL07427]
- DIVISION OF LUNG DISEASES [N01HR016049] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL086601, R01HL066289, T32HL007427, R37HL066289, P01HL083069, K08HL092222, P50HL067664, U01HL065899, K01HL004370, U01HL075419] Funding Source: NIH RePORTER
Rationale: Polymorphisms in the gene for transforming growth factor-beta 1 (TGFBI) 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 TGFBI 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 <= 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 TGFBI SNPs on airway responsiveness and asthma exacerbations.
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