Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations
Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations
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DOI：
10.1016/s0091-6749(03)01939-0
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发表时间：
2003-10-01
影响因子：
14.2
通讯作者：
Meyers, DA
中科院分区：
文献类型：
--
作者：
Howard, TD;Postma, DS;Meyers, DA
背景资料：哮喘是一种复杂的遗传性疾病，其特征是可逆的间歇性气道阻塞和呼吸道症状，主要由急性和慢性支气管炎症引起。最近，一个可能参与气道重塑的基因，解整合素和金属蛋白酶33（ADAM 33），被认为与哮喘易感性有关。目的：我们试图确定是否与哮喘或密切相关的表型在4个不同的哮喘population.Methods：8个单核苷酸多态性（SNPs）在3'部分的ADAM 33在4个独特的哮喘人群（非洲裔美国人，美国白色，美国西班牙裔，荷兰白色）进行了评估。这些SNPs先前被报道与哮喘在白色人群从美国和英国。结果：显着的协会观察到至少一个SNP和哮喘在每个人群（P = 0.0009 - 0.04）。相关表型包括血清总IgE水平和皮肤试验反应性也相关（P = 0.003 - 0.05）。然而，没有单一SNP在所有人群中相关。此外，单倍型分析显示，没有一个单倍型占哮喘易感风险，虽然潜在的风险单倍型存在于一些population.Conclusion：复制原来的ADAM 33的研究结果在这4个额外的哮喘人群表明，这个基因（也许其他人与它相互作用）是重要的哮喘的发展和发病机制。
Background: Asthma is a complex genetic disease characterized by reversible intermittent airway obstruction and respiratory symptoms primarily caused by acute and chronic bronchial inflammation. Recently, a gene potentially involved in airway remodeling, a disintegrin and metalloprotease 33 (ADAM33), was implicated in asthma susceptibility. Objective: We sought to determine whether polymorphisms in ADAM33 are associated with asthma or closely related phenotypes in 4 different asthma populations.Methods: Eight single nucleotide polymorphisms (SNPs) were evaluated in the 3' portion of ADAM33 in 4 unique asthma populations (African American, US white, US Hispanic, and Dutch white). These SNPs were previously reported to be associated with asthma in white populations from the United States and United Kingdom.Results: Significant associations were observed with at least one SNP and asthma in each population (P = .0009-.04). Related phenotypes that included total serum IgE levels and skin test responsiveness were also associated (P = .003-.05). However, no single SNP was associated across all populations. Additionally, haplotype analysis revealed that no single haplotype accounted for asthma susceptibility risk, although potential risk haplotypes existed within some of the populations.Conclusion: Replication of the original ADAM33 findings in these 4 additional asthma populations suggests that this gene (and perhaps others that interact with it) is important in the development and pathogenesis of asthma.