Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:130

Article

Daley, Denise¹  Park, Julie E.¹  He, Jian-Qing¹  Yan, Jin¹  Akhabir, Loubna¹  Stefanowicz, Dorota¹  Becker, Allan B.^2,3  Chan-Yeung, Moira⁴  Bosse, Yohan^5,6  Kozyrskyj, Anita L.^7,8  James, Alan L.⁹  Musk, Arthur W.¹⁰  Laprise, Catherine^11,12  Hegele, Richard G.¹³  Pare, Peter D.^1,14  Sandford, Andrew J.^1,14 

[1] Univ British Columbia, James Hogg Res Ctr, Inst Heart & Lung Hlth, Vancouver, BC V6Z 1Y6, Canada

[2] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada

[3] Univ Manitoba, Manitoba Inst Child Hlth, Winnipeg, MB R3T 2N2, Canada

[4] Univ British Columbia, Occupat & Environm Lung Dis Unit, Vancouver, BC V6Z 1Y6, Canada

[5] Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada

[6] Univ Laval, Dept Mol Med, Ste Foy, PQ G1K 7P4, Canada

[7] Univ Alberta, Dept Pediat, Fac Med & Dent, Edmonton, AB, Canada

[8] Univ Manitoba, Dept Pediat & Child Hlth, Fac Med, Winnipeg, MB R3T 2N2, Canada

[9] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Perth, WA, Australia

[10] Sir Charles Gairdner Hosp, Dept Resp Med, Perth, WA, Australia

[11] Univ Quebec Chicoutimi, Dept Sci Fondamentales, Saguenay, PQ, Canada

[12] Univ Montreal, Chicoutimi Hosp, Community Genom Med Ctr, Saguenay, PQ, Canada

[13] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[14] Univ British Columbia, Dept Med, Div Resp Med, Vancouver, BC V6Z 1Y6, Canada

关键词: Asthma;    atopy;    atopic asthma;    airway hyperresponsiveness;    genetics;    association;    gene-environment interactions;    viral exposures;   

DOI  :  10.1016/j.jaci.2012.07.051

来源: Elsevier

【 摘 要 】

Background: The innate immune system is essential for host survival because of its ability to recognize invading pathogens and mount defensive responses. Objectives: We sought to identify genetic associations of innate immunity genes with atopy and asthma and interactions with early viral infections (first 12 months of life) in a high-risk birth cohort. Methods: Three Canadian family-based studies and 1 Australian population-based case-control study (n = 5565) were used to investigate associations of 321 single nucleotide polymorphisms (SNPs) in 26 innate immunity genes with atopy, asthma, atopic asthma, and airway hyperresponsiveness. Interactions between innate immunity genes and early viral exposure to 3 common viruses (parainfluenza, respiratory syncytial virus, and picornavirus) were examined in the Canadian Asthma Primary Prevention Study by using both an affected-only family-based transmission disequilibrium test and case-control methods. Results: In a joint analysis of all 4 cohorts, IL-1 receptor 2 (IL1R2) and Toll-like receptor 1 (TLR1) SNPs were associated with atopy after correction for multiple comparisons. In addition, an NFKBIA SNP was associated with atopic asthma. Six SNPs (rs1519309 [TLR3], rs740044 [ILIR2], rs4543123 [TLR1], rs5741812 [LBP], rs917998 [IL18RAP], and rs3136641 [NFKBIB]) were significant (P < .05, confirmed with 30,000 permutations) in both the combined analysis of main genetic effects and SNP-virus interaction analyses in both case-control and family-based methods. The TLR1 variant (rs4543123) was associated with both multiple viruses (respiratory syncytial virus and parainfluenza virus) and multiple phenotypes. Conclusion: We have identified novel susceptibility genes for asthma and related traits and interactions between these genes and early-life viral infections. (J Allergy Clin Immunol 2012;130:1284-93.)

【 授权许可】

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