Holgate Stephen T, Yang Youwen, Haitchi Hans-Michael, Powell Rob M, Holloway John W, Yoshisue Hajime, Pang Yun Yun, Cakebread Julie, Davies Donna E
Infection, Inflammation, and Repair Division, MP810, F Level, South Block, Southampton General Hospital, Southampton SO16 6YD, UK.
Proc Am Thorac Soc. 2006 Jul;3(5):440-3. doi: 10.1513/pats.200603-026AW.
The ability to identify novel disease genes by positional cloning led to the identification of a disintegrin and metalloprotease (ADAM)33 gene on chromosome 20p13 as a susceptibility gene for asthma. Case-control and family-based association studies have mostly confirmed a link between ADAM33 and asthma. Its restricted expression to mesenchymal cells as well as its association with bronchial hyperresponsiveness and accelerated decline in lung function over time point strongly to its involvement in the structural airway components of asthma, such as remodeling. Extensive alternative splicing, expression during branching morphogensis in the developing fetus, impaired lung function in childhood, the production of a soluble form linked to chronic asthma, and tight epigenetic regulation indicate a level of complexity in the way ADAM33 influences disease phenotype. Its recent association with chronic obstructive pulmonary disease as well as with asthma and lung development points to functions relating to airway wall modeling and remodeling as a general morphogenetic repair gene rather than being restricted to asthma.
通过定位克隆识别新型疾病基因的能力，使得位于20号染色体p13上的一种解整合素和金属蛋白酶（ADAM）33基因被鉴定为哮喘的易感基因。病例对照研究和基于家系的关联研究大多证实了ADAM33与哮喘之间的联系。它在间充质细胞中的表达受限，以及与支气管高反应性和肺功能随时间加速下降的关联，强烈表明它参与了哮喘的气道结构成分，如重塑。广泛的可变剪接、在发育中的胎儿分支形态发生过程中的表达、儿童期肺功能受损、与慢性哮喘相关的可溶性形式的产生以及严格的表观遗传调控，表明ADAM33影响疾病表型的方式具有一定的复杂性。它最近与慢性阻塞性肺疾病以及哮喘和肺发育的关联，表明其作为一种一般的形态发生修复基因，与气道壁建模和重塑有关，而不仅限于哮喘。
