Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes
Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes
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DOI：
10.1016/j.jaci.2012.07.051
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发表时间：
2012-12-01
影响因子：
14.2
通讯作者：
Sandford, Andrew J.
中科院分区：
文献类型：
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作者：
Daley, Denise;Park, Julie E.;Sandford, Andrew J.
工作背景：先天免疫系统是宿主生存所必需的，因为它能够识别入侵的病原体并启动防御反应。目的：我们试图确定先天免疫基因与特应性和哮喘的遗传关联以及与早期病毒感染的相互作用（出生后前12个月）的高危出生队列。3项加拿大基于家庭的研究和1项澳大利亚基于人群的病例对照研究（n = 5565）研究了26个先天免疫基因的321个单核苷酸多态性（SNP）与特应性、哮喘、特应性哮喘和气道高反应性。先天免疫基因与3种常见病毒早期暴露的相互作用在加拿大哮喘一级预防研究中，通过使用仅受影响的基于家庭的传播不平衡检验和病例对照方法，检查了副流感病毒、呼吸道合胞病毒和小核糖核酸病毒。在所有4个队列的联合分析中，在校正多重比较后，IL-1受体2（IL 1 R2）和Toll样受体1（TLR 1）SNP与特应性相关。此外，NFKBIA SNP与特应性哮喘相关。6个SNP（rs 1519309 [TLR 3]、rs740044 [ILIR 2]、rs 4543123 [TLR 1]、rs 5741812 [LBP]、rs 917998 [IL 18 RAP]和rs3136641 [NFKBIB]）显著（P <0.05，证实为30，000个排列）的主要遗传效应的联合分析和SNP-病毒相互作用分析的病例对照和家庭为基础的方法。TLR 1变异体（rs 4543123）与多种病毒（呼吸道合胞病毒和副流感病毒）和多种表型（phenotypes.Conclusion）相关，我们发现了新的哮喘易感基因和相关性状，以及这些基因与早期病毒感染之间的相互作用。（J Allergy Clin Immunol 2012;130：1284-93.）
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.)