Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
Int Arch Allergy Immunol. 2010;152(1):32-40. doi: 10.1159/000260081. Epub 2009 Nov 24.
A disintegrin and metalloprotein-33 (ADAM33) participates in the bronchial remodeling process in asthma, and genetic analyses pointed it out as a candidate gene in asthma.
To analyze the association between ADAM33 and asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia, we genotyped 6 single-nucleotide polymorphisms of ADAM33 in 429 asthmatics, 401 controls and 116 family trios using fluorogenic probes. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Case-control and family-based analyses were performed. Case-control association analyses were corrected by population stratification using a set of 52 ancestry-informative markers.
Eight common haplotypes were identified; among them, H4 (GCAGGG) was associated with asthma in the family group (Z score: -2.049, p = 0.04). We also found an association between the TT genotype of ST+7 and asthma in the case-control study (p = 0.05) that disappeared after correcting for multiple testing. In the family-based analysis, this genotype was a risk factor for asthma (p = 0.01), high total IgE (Z score: 2.546, p = 0.01) and high specific IgE against B. tropicalis (p = 0.02) and D. pteronyssinus (Z score: 2.414, p = 0.01). V4 was associated with specific IgE against B. tropicalis (p = 0.03); T2 with asthma (p = 0.03), high total IgE (p = 0.02) and IgE against D. pteronyssinus (p = 0.03) and T1 with high total IgE (p = 0.04). None of these associations was maintained after correction for multiple testing.
Our findings suggest a relevant role of ADAM33 in thepathogenesis of asthma in this population.
解整合素金属蛋白酶 33（ADAM33）参与哮喘的支气管重塑过程，遗传分析将其作为哮喘的候选基因。
为了分析 ADAM33 与哮喘以及哥伦比亚加勒比海岸人群总 IgE 和螨特异性 IgE 水平之间的关系，我们使用荧光探针对 429 例哮喘患者、401 例对照者和 116 个家系三代中的 6 个 ADAM33 单核苷酸多态性进行了基因分型。采用 ELISA 法测定对 Blomia tropicalis 和 Dermatophagoides pteronyssinus 的总 IgE 和特异性 IgE。进行病例对照和家系研究。通过一组 52 个祖先信息标记物进行病例对照关联分析，对人群分层进行校正。
确定了 8 个常见单倍型；其中，H4（GCAGGG）与家系组中的哮喘相关（Z 评分：-2.049，p=0.04）。我们还发现病例对照研究中 ST+7 的 TT 基因型与哮喘之间存在关联（p=0.05），但经多次检验校正后消失。在家系研究中，该基因型是哮喘的危险因素（p=0.01），总 IgE 水平高（Z 评分：2.546，p=0.01），对 B. tropicalis 和 D. pteronyssinus 的特异性 IgE 水平高（Z 评分：2.414，p=0.01）。V4 与对 B. tropicalis 的特异性 IgE 相关（p=0.03）；T2 与哮喘（p=0.03）、总 IgE 水平高（p=0.02）和对 D. pteronyssinus 的 IgE 相关（p=0.03）以及 T1 与总 IgE 水平高相关（p=0.04）。在进行多次检验校正后，这些关联均不再成立。
本研究结果提示 ADAM33 在该人群哮喘发病机制中起重要作用。
