Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2005 Apr;60(4):274–276. doi: 10.1136/thx.2004.027227

Contribution of ADAM33 polymorphisms to the population risk of asthma

J Blakey 1, E Halapi 1, U Bjornsdottir 1, A Wheatley 1, S Kristinsson 1, R Upmanyu 1, K Stefansson 1, H Hakonarson 1, I Hall 1
PMCID: PMC1747383  PMID: 15790980

Abstract

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.

Full Text

The Full Text of this article is available as a PDF (82.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cookson William. A new gene for asthma: would you ADAM and Eve it? Trends Genet. 2003 Apr;19(4):169–172. doi: 10.1016/S0168-9525(03)00025-8. [DOI] [PubMed] [Google Scholar]
  2. Gretarsdottir Solveig, Thorleifsson Gudmar, Reynisdottir Sigridur Th, Manolescu Andrei, Jonsdottir Sif, Jonsdottir Thorbjörg, Gudmundsdottir Thorunn, Bjarnadottir Sigrun M., Einarsson Olafur B., Gudjonsdottir Herdis M. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet. 2003 Sep 21;35(2):131–138. doi: 10.1038/ng1245. [DOI] [PubMed] [Google Scholar]
  3. Hakonarson Hakon, Bjornsdottir Unnur S., Halapi Eva, Palsson Snaebjorn, Adalsteinsdottir Elva, Gislason David, Finnbogason Gudmundur, Gislason Thorarinn, Kristjansson Kristleifur, Arnason Thor. A major susceptibility gene for asthma maps to chromosome 14q24. Am J Hum Genet. 2002 Jul 15;71(3):483–491. doi: 10.1086/342205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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. Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations. J Allergy Clin Immunol. 2003 Oct;112(4):717–722. doi: 10.1016/s0091-6749(03)01939-0. [DOI] [PubMed] [Google Scholar]
  5. Jongepier H., Boezen H. M., Dijkstra A., Howard T. D., Vonk J. M., Koppelman G. H., Zheng S. L., Meyers D. A., Bleecker E. R., Postma D. S. Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma. Clin Exp Allergy. 2004 May;34(5):757–760. doi: 10.1111/j.1365-2222.2004.1938.x. [DOI] [PubMed] [Google Scholar]
  6. Lee J. H., Park H-S, Park S. W., Jang A. S., Uh S. T., Rhim T., Park C-S, Hong S-J, Holgate S. T., Holloway J. W. ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics. Clin Exp Allergy. 2004 Jun;34(6):860–865. doi: 10.1111/j.1365-2222.2004.01977.x. [DOI] [PubMed] [Google Scholar]
  7. Lind Denise L., Choudhry Shweta, Ung Ngim, Ziv Elad, Avila Pedro C., Salari Keyan, Ha Connie, Lovins Elizabeth G., Coyle Natasha E., Nazario Sylvette. ADAM33 is not associated with asthma in Puerto Rican or Mexican populations. Am J Respir Crit Care Med. 2003 Sep 4;168(11):1312–1316. doi: 10.1164/rccm.200306-877OC. [DOI] [PubMed] [Google Scholar]
  8. Powell Robert M., Wicks James, Holloway John W., Holgate Stephen T., Davies Donna E. The splicing and fate of ADAM33 transcripts in primary human airways fibroblasts. Am J Respir Cell Mol Biol. 2004 Jan 23;31(1):13–21. doi: 10.1165/rcmb.2003-0330OC. [DOI] [PubMed] [Google Scholar]
  9. Raby Benjamin A., Silverman Edwin K., Kwiatkowski David J., Lange Christoph, Lazarus Ross, Weiss Scott T. ADAM33 polymorphisms and phenotype associations in childhood asthma. J Allergy Clin Immunol. 2004 Jun;113(6):1071–1078. doi: 10.1016/j.jaci.2004.03.035. [DOI] [PubMed] [Google Scholar]
  10. Umland Shelby P., Garlisi Charles G., Shah Himanshu, Wan Yuntao, Zou Jun, Devito Kristine E., Huang Whei-Mei, Gustafson Eric L., Ralston Robert. Human ADAM33 messenger RNA expression profile and post-transcriptional regulation. Am J Respir Cell Mol Biol. 2003 May 30;29(5):571–582. doi: 10.1165/rcmb.2003-0028OC. [DOI] [PubMed] [Google Scholar]
  11. Van Eerdewegh Paul, Little Randall D., Dupuis Josée, Del Mastro Richard G., Falls Kathy, Simon Jason, Torrey Dana, Pandit Sunil, McKenny Joyce, Braunschweiger Karen. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature. 2002 Jul 10;418(6896):426–430. doi: 10.1038/nature00878. [DOI] [PubMed] [Google Scholar]
  12. Werner M., Herbon N., Gohlke H., Altmüller J., Knapp M., Heinrich J., Wjst M. Asthma is associated with single-nucleotide polymorphisms in ADAM33. Clin Exp Allergy. 2004 Jan;34(1):26–31. doi: 10.1111/j.1365-2222.2004.01846.x. [DOI] [PubMed] [Google Scholar]
  13. White Judith M. ADAMs: modulators of cell-cell and cell-matrix interactions. Curr Opin Cell Biol. 2003 Oct;15(5):598–606. doi: 10.1016/j.ceb.2003.08.001. [DOI] [PubMed] [Google Scholar]
  14. Zou Jun, Zhu Feng, Liu Jianjun, Wang Wenyan, Zhang Rumin, Garlisi Charles G., Liu Yan-Hui, Wang Shihong, Shah Himanshu, Wan Yuntao. Catalytic activity of human ADAM33. J Biol Chem. 2003 Dec 15;279(11):9818–9830. doi: 10.1074/jbc.M309696200. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES