Contribution of ADAM33 polymorphisms to the population risk of asthma
Contribution of ADAM33 polymorphisms to the population risk of asthma
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DOI：
10.1136/thx.2004.027227
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发表时间：
2005-04-01
期刊：
影响因子：
10
通讯作者：
Hall, IP
中科院分区：
文献类型：
--
作者：
Blakey, J;Halapi, E;Hall, IP
背景：adam33是首个通过定位克隆技术确定的哮喘候选基因，相关研究达到了令人印象深刻的统计学意义。它在肌肉形成、气道建模和通过蛋白质脱落的信号传导中具有假定的作用。对最初研究方法的担忧导致了几次重复的尝试，结果不一致。方法：为了明确ADAM33在确定普通人群哮喘风险中的作用，在对所有现有数据进行荟萃分析之后，进行了新的传播不平衡和病例对照研究。结果：对冰岛和英国人群的研究表明，如果单独考虑，没有关联。然而，荟萃分析显示，在这两种类型的研究中，F+ 1和ST+ 7变异与哮喘显著相关。结论：仅在英国，这种变异所带来的额外风险就会导致5万例哮喘病例。这项研究也证明了充分调查这些假设所需的研究规模。
Background: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results.Method: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case- control studies were undertaken followed by a meta- analysis of all existing data.Results: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta- analysis, however, showed that the F+ 1 and ST+ 7 variants were significantly associated with asthma in both types of study.Conclusions: The additional risk imparted by this variation would account for 50 000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.