17q12-21 and asthma: interactions with early-life environmental exposures

被引：34

作者：

Blekic, Mario ^{[1
]}

Bukvic, Blazenka Kljaic ^{[1
]}

Aberle, Neda ^{[1
]}

Marinho, Susana ^{[2
]}

Hankinson, Jenny ^{[2
]}

Custovic, Adnan ^{[2
]}

Simpson, Angela ^{[2
]}

机构：

[1] Univ Osijek, Gen Hosp Dr Josip Bencevic Slavonski Brod, Osijek, Croatia

[2] Univ Manchester, Univ Hosp South Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Ctr Resp & Allergy, Manchester M23 9LT, Lancs, England

来源：

ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY | 2013年 / 110卷 / 05期

关键词：

FALSE DISCOVERY RATE; ORMDL3; EXPRESSION; SMOKING EXPOSURE; TOBACCO-SMOKE; GENE; 17Q21; VARIANTS; GENOME; ONSET; POLYMORPHISMS;

D O I：

10.1016/j.anai.2013.01.021

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: 17q12-21 polymorphisms are associated with asthma presence and severity across different populations. Objective: To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures. Methods: We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry. Results: We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation. Conclusion: Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies. (c) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

引用

页码：347 / +

页数：9

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