Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure. Issue 1 (20th January 2013)

• Record Type: Journal Article
• Authors: Bukvic, Blazenka Kljaic; Blekic, Mario; Simpson, Angela; Marinho, Susana; Curtin, John A.; Hankinson, Jenny; Aberle, Neda; Custovic, Adnan
• Is Part Of: Pediatric allergy and immunology. Volume 24:Issue 1(2013)
• Page Start: 10
• Page End: 18
• Publication Date: 2013-01-20
• Subjects: Allergy in children -- Periodicals; Immunologic diseases in children -- Periodicals; 617
• DOI: 10.1111/pai.12019
• Languages: English
• ISSNs: 0905-6157

Abstract

<abstract abstract-type="main" id="pai12019-abs-0001"> <title>Abstract</title> <sec id="pai12019-sec-0001" sec-type="section"> <title>Background</title> <p>We investigated the association between genetic variation in chromosomal region 20p13‐p12 (<italic>ADAM33</italic> and flanking genes <italic>ATRN</italic>, <italic> GFRA4</italic>, <italic> SIGLEC1</italic> and <italic>HSPA12B</italic>) 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.</p> </sec> <sec id="pai12019-sec-0002" sec-type="section"> <title>Methods</title> <p>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 (SNPs) in the analysis.</p> </sec> <sec id="pai12019-sec-0003" sec-type="section"> <title>Results</title> <p>Seventeen SNPs were significantly associated with asthma; one (rs41534847 in <italic>ADAM33</italic>) remained significant after correction for multiple testing. Thirty‐six SNPs were significantly associated with lung function, of which 15 (six <italic>ARTN</italic>, three <italic>ADAM33</italic>, five <italic>SIGLEC1</italic> and one <italic>HSPA12B)</italic> remained significant after correction. We observed a significant interaction between 23 SNPs and early‐life ETS exposure in relation to lung function measures. For example, for rs512625 in <italic>ADAM33</italic>, there was significant interaction with ETS exposure in relation to hospitalisations (p<sub>int</sub> = 0.02) and lung function (p<sub>int</sub> = 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.</p> </sec> <sec id="pai12019-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>