Howard Timothy D, Postma Dirkje S, Jongepier Hajo, Moore Wendy C, Koppelman Gerard H, Zheng Siqun L, Xu Jianfeng, Bleecker Eugene R, Meyers Deborah A
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Allergy Clin Immunol. 2003 Oct;112(4):717-22. doi: 10.1016/s0091-6749(03)01939-0.
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.
We sought to determine whether polymorphisms in ADAM33 are associated with asthma or closely related phenotypes in 4 different asthma populations.
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.
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.
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.
哮喘是一种复杂的遗传性疾病，其特征为可逆性间歇性气道阻塞以及主要由急慢性支气管炎症引起的呼吸道症状。最近，一种可能参与气道重塑的基因——解整合素金属蛋白酶33（ADAM33），被认为与哮喘易感性有关。
我们试图确定ADAM33基因多态性是否与4种不同哮喘人群中的哮喘或密切相关表型相关。
在4个独特的哮喘人群（非裔美国人、美国白人、美国西班牙裔和荷兰白人）中，对ADAM33基因3'端的8个单核苷酸多态性（SNP）进行了评估。这些SNP先前报道在美国和英国的白人人群中与哮喘相关。
在每个群体中，至少有一个SNP与哮喘存在显著关联（P = 0.0009 - 0.04）。包括总血清IgE水平和皮肤试验反应性在内的相关表型也存在关联（P = 0.003 - 0.05）。然而，没有一个SNP在所有群体中都与哮喘相关。此外，单倍型分析显示，虽然在一些群体中存在潜在的风险单倍型，但没有一个单倍型能解释哮喘易感性风险。
在这4个额外的哮喘人群中重复最初关于ADAM33的研究结果表明，该基因（以及可能与其相互作用的其他基因）在哮喘的发生发展和发病机制中起重要作用。
