固有免疫基因变异体与哮喘和湿疹相关
2012/01/31
摘要
背景：固有免疫通路在哮喘和湿疹的致病当中具有重要作用。然而，仅发现这些基因中的某些与上述疾病相关。本研究在哮喘和湿疹儿童中，研究固有免疫通路相关基因的多态性。此外，通过多变量分析，比较各基因与疾病的相关性。
方法：采用新的方法---病例对照为基础的相关检测（C2BAT），对44个固有免疫基因的569个单核苷酸多态性（SNPs）进行检测，分析其与哮喘和湿疹的关系。入选的哮喘和湿疹患儿来自于波斯顿家庭过敏原和哮喘研究以及康涅狄格州儿童哮喘研究。筛选用于鉴别与哮喘和湿疹最为相关的SNPs。随后，通过贝叶斯网络研究固有免疫相关基因变异体与哮喘和湿疹风险的相互作用。
结果：在多次比较校正后，6个基因（CARD25、TGFB1、LY96、ACAA1、DEFB1、IFNG）的7个SNPs与哮喘相关（校正后P<0.02），而3个不同基因（CD80、STAT4、IRAKI）的5个SNPs与湿疹显著相关（校正后P<0.02）。没有SNPs同时与哮喘和湿疹相关。贝叶斯网络寻找的基因中，在单个SNP研究中，仅CD80与湿疹相关。采用的新方法，允许在同一人群中筛选和复制。以此，我们发现了固有免疫与哮喘和湿疹的关系。贝叶斯网络分析显示，SNPs通过其相互作用，影响着疾病的易感性。
结论：固有免疫基因与哮喘和湿疹的致病相关，这两种疾病可能有着不一样的遗传决定因素。
（刘国梁 审校）
Pediatr Allergy Immunol. 2011 Dec 23. doi: 10.1111/j. 1399-3038. 2011. 01243.x. [Epub ahead of print]
Association of variants in innate immune genes with asthma and eczema.
Sharma S, Poon A, Himes BE, Lasky-Su J, Sordillo JE, Belanger K, Milton DK, Bracken MB, Triche EW, Leaderer BP, Gold DR, Litonjua AA.
Source
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA University of Maryland School of Public Health, College Park, MD, USA Department of Community Health and Epidemiology, Brown University School of Medicine, Providence, RI, USA.
Abstract
BACKGROUND: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach.
METHODS: Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks.
RESULTS: After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions.
CONCLUSION: Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
Pediatr Allergy Immunol. 2011 Dec 23. doi: 10.1111/j. 1399-3038. 2011. 01243.x. [Epub ahead of print]
