Association of variants in innate immune genes with asthma and eczema

作者：Sharma Sunita^*; Poon Audrey; Himes Blanca E; Lasky Su Jessica; Sordillo Joanne E; Belanger Kathleen; Milton Donald K; Bracken Michael B; Triche Elizabeth W; Leaderer Brian P; Gold Diane R; Litonjua Augusto A

来源：Pediatric Allergy and Immunology, 2012, 23(4): 315-323.

DOI：10.1111/j.1399-3038.2011.01243.x

• asthma
• Bayesian network
• genetic association
• eczema
• innate immunity

To cite this article: 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. Association of variants in innate immune genes with asthma and eczema. Pediatric Allergy Immunology 2012: 23: 315323. 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.

• 出版日期2012-6