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Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure
Author(s) -
Bukvic Blazenka Kljaic,
Blekic Mario,
Simpson Angela,
Marinho Susana,
Curtin John A.,
Hankinson Jenny,
Aberle Neda,
Custovic Adnan
Publication year - 2013
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12019
Subject(s) - medicine , single nucleotide polymorphism , asthma , snp , tobacco smoke , context (archaeology) , exacerbation , allele , bronchial hyperresponsiveness , passive smoking , immunology , lung , genotype , respiratory disease , genetics , gene , pathology , biology , environmental health , paleontology
Background We investigated the association between genetic variation in chromosomal region 20p13‐p12 ( ADAM 33 and flanking genes ATRN , GFRA 4 , SIGLEC 1 and HSPA 12 B ) and asthma. Amongst asthmatics, we then investigated the association between genetic variants and asthma severity. We evaluated the effect of environmental tobacco smoke ( ETS ) exposure in the context of genetic variants. Methods In a case–control study, we recruited 423 asthmatic children and 414 non‐asthmatic controls (age 5–18 yr). Amongst asthmatics, we measured lung function and extracted data on hospitalisation for asthma exacerbation from medical records. Early‐life ETS exposure was assessed by questionnaire. We included 85 single‐nucleotide polymorphisms ( SNP s) in the analysis. Results Seventeen SNP s were significantly associated with asthma; one (rs41534847 in ADAM 33 ) remained significant after correction for multiple testing. Thirty‐six SNP s were significantly associated with lung function, of which 15 (six ARTN , three ADAM 33 , five SIGLEC 1 and one HSPA 12 B ) remained significant after correction. We observed a significant interaction between 23 SNP s and early‐life ETS exposure in relation to lung function measures. For example, for rs512625 in ADAM 33 , there was significant interaction with ETS exposure in relation to hospitalisations (p int  = 0.02) and lung function (p int  = 0.03); G ‐allele homozygotes had a 9.15‐fold [95% CI 2.28–36.89] higher risk of being hospitalized and had significantly poorer lung function if exposed to ETS , with no effect of ETS exposure amongst A ‐allele carriers. Conclusion We demonstrated several novel significant interactions between polymorphisms in 20p13‐p12 and early‐life ETS exposure with asthma presence and, amongst asthmatics, a significant association with the severity of their disease.

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