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T1 polymorphism in a disintegrin and metalloproteinase 33 (ADAM33) gene may contribute to the risk of childhood asthma in Asians

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Abstract

Objective

Polymorphisms in ADAM33 gene have been implicated in susceptibility to the risk of childhood asthma. However, the results remain controversial. We performed meta-analyses to clarify the relationship between them.

Methods

Relevant articles were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. The Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations.

Results

Fourteen studies with five ADAM33 polymorphisms (F + 1, T1, T2, S2, and V4) were identified, involving 2687 cases and 2996 controls. ADAM33 F + 1, T2, and T1 polymorphisms showed significant associations with asthma risks in the overall and Caucasian children, Asian children, and Caucasian and Chinese children, respectively; however, these significant results were unstable in sensitivity analysis. T1 revealed significant and stable associations with asthma risks among Asian children in the dominant (OR = 2.00, 95% CI = 1.40–2.87, P = 0.0002) and codominant (OR = 3.06, 95% CI = 1.71–5.50, P = 0.0002) models; in cumulative meta-analyses, these significant results were robust. Concerning S2 or V4 polymorphism, no significant associations were observed.

Conclusion

These findings demonstrate that ADAM33 T1 polymorphism might be a potential susceptible predictor of asthma for Asian children. Further functional studies between this polymorphism and asthma risks are warranted.

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References

  1. Yang Y, Wicks J, Haitchi HM, Powell RM, Manuyakorn W, Howarth PH, et al. Regulation of a disintegrin and metalloprotease-33 expression by transforming growth factor-beta. Am J Respir Cell Mol Biol. 2012;46(5):633–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Grotenboer NS, Ketelaar ME, Koppelman GH, Nawijn MC. Decoding asthma: translating genetic variation in IL33 and IL1RL1 into disease pathophysiology. J Allergy Clin Immunol. 2013;131(3):856–65.

    Article  CAS  PubMed  Google Scholar 

  3. Pinto LA, Stein RT, Kabesch M. Impact of genetics in childhood asthma. J Pediatr (Rio J). 2008;84(4 Suppl):S68–75.

    Article  Google Scholar 

  4. Ortiz RA, Barnes KC. Genetics of allergic diseases. Immunol Allergy Clin North Am. 2015;35(1):19–44.

    Article  PubMed  Google Scholar 

  5. Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature. 2002;418(6896):426–30.

    Article  PubMed  Google Scholar 

  6. Jie Z, Jin M, Cai Y, Bai C, Shen Y, Yuan Z, et al. The effects of Th2 cytokines on the expression of ADAM33 in allergen-induced chronic airway inflammation. Respir Physiol Neurobiol. 2009;168(3):289–94.

    Article  CAS  PubMed  Google Scholar 

  7. Lee JY, Park SW, Chang HK, Kim HY, Rhim T, Lee JH, et al. A disintegrin and metalloproteinase 33 protein in patients with asthma: relevance to airflow limitation. Am J Respir Crit Care Med. 2006;173(7):729–35.

    Article  CAS  PubMed  Google Scholar 

  8. Foley SC, Mogas AK, Olivenstein R, Fiset PO, Chakir J, Bourbeau J, et al. Increased expression of ADAM33 and ADAM8 with disease progression in asthma. J Allergy Clin Immunol. 2007;119(4):863–71.

    Article  CAS  PubMed  Google Scholar 

  9. Ito I, Laporte JD, Fiset PO, Asai K, Yamauchi Y, Martin JG, et al. Downregulation of a disintegrin and metalloproteinase 33 by IFN-gamma in human airway smooth muscle cells. J Allergy Clin Immunol. 2007;119(1):89–97.

    Article  CAS  PubMed  Google Scholar 

  10. Kavvoura FK, Ioannidis JP. Methods for meta-analysis in genetic association studies: a review of their potential and pitfalls. Hum Genet. 2008;123(1):1–14.

    Article  PubMed  Google Scholar 

  11. Blakey J, Halapi E, Bjornsdottir US, Wheatley A, Kristinsson S, Upmanyu R, et al. Contribution of ADAM33 polymorphisms to the population risk of asthma. Thorax. 2005;60(4):274–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee YH, Song GG. Association between ADAM33 T1 polymorphism and susceptibility to asthma in Asians. Inflamm Res. 2012;61(12):1355–62.

    Article  CAS  PubMed  Google Scholar 

  13. Song GG, Kim JH, Lee YH. Association between ADAM33 S2 and ST+ 4 polymorphisms and susceptibility to asthma: a meta-analysis. Gene. 2013;524(1):72–8.

    Article  CAS  PubMed  Google Scholar 

  14. Zheng W, Wang L, Su X, Hu XF. Association between V4 polymorphism in the ADAM33 gene and asthma risk: a meta-analysis. Genet Mol Res. 2015;14(1):989–99.

    Article  CAS  PubMed  Google Scholar 

  15. Liu Y, Wang ZH, Zhen W, Lu SJ, Liu Z, Zou LY, et al. Association between genetic polymorphisms in the ADAM33 gene and asthma risk: a meta-analysis. DNA Cell Biol. 2014;33(11):793–801.

    Article  CAS  PubMed  Google Scholar 

  16. Liang S, Wei X, Gong C, Wei J, Chen Z, Deng J. A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis. Hum Immunol. 2013;74(5):648–57.

    Article  CAS  PubMed  Google Scholar 

  17. Li X, Zhang Y, Zhang J, Xiao Y, Huang J, Tian C, et al. Asthma susceptible genes in Chinese population: a meta-analysis. Respir Res. 2010;11:129.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bora E, Arikan-Ayyildiz Z, Firinci F, Cankaya T, Giray-Bozkaya O, Uzuner N, et al. ADAM33 gene polymorphisms are not associated with asthma in turkish children. Ped Allergy Immunol Pulmonol. 2012;25(2):97–100.

    Article  Google Scholar 

  19. Murk W, Walsh K, Hsu LI, Zhao L, Bracken MB, Dewan AT. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum Hered. 2011;71(2):97–105.

    Article  PubMed  Google Scholar 

  20. Al-Khayyat AI, Al-Anazi M, Warsy A, Vazquez-Tello A, Alamri AM, Halwani R, et al. T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma in a Saudi Arabian population: a pilot study. Ann Saudi Med. 2012;32(5):479–86.

    Article  PubMed  Google Scholar 

  21. El-Falaki MM, Wilson MM, Ezzat GM, Mokhtar DA, El Baz MS, Hamed DH. A disintegrin and metalloproteinase 33 (ADAM33) gene polymorphism association with asthma in Egyptian children. Egypt J Med Hum Genet. 2013;14(1):55–62.

    Article  Google Scholar 

  22. Li H, Li Y, Zhang M, Xu G, Feng X, Xi J, et al. Associations of genetic variants in ADAM33 and TGF-beta1 genes with childhood asthma risk. Biomed Rep. 2014;2(4):533–8.

    PubMed  PubMed Central  Google Scholar 

  23. Fan JG, Wang ZA, Zhao HX. The ADAM33 S2 polymorphism is associated with susceptibility to pediatric asthma in the Chinese Han population. Genet Test Mol. Biomarkers. 2015;19(10):573–8.

    CAS  Google Scholar 

  24. Shalaby SM, Abdul-Maksoud RS, Abdelsalam SM, Abdelrahman HM, Abdelaziz Almalky MA. ADAM33 and ADAM12 genetic polymorphisms and their expression in Egyptian children with asthma. Ann Allergy Asthma Immunol. 2016;116(1):31–6.

    Article  CAS  PubMed  Google Scholar 

  25. Zihlif M, Zihlif N, Obeidat NM, Mahafza T, Froukh T, Ghanim MT, et al. Association between ADAM33 polymorphisms and susceptibility with adult and childhood asthma among Jordanians. Genet Test Mol Biomark. 2014;18(11):767–74.

    Article  CAS  Google Scholar 

  26. Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med. 1992;327(4):248–54.

    Article  CAS  PubMed  Google Scholar 

  27. Rotondi MA, Bull SB. Cumulative meta-analysis for genetic association: when is a new study worthwhile? Hum Hered. 2012;74(2):61–70.

    Article  CAS  PubMed  Google Scholar 

  28. Zintzaras E, Lau J. Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol. 2008;61(7):634–45.

    Article  PubMed  Google Scholar 

  29. Zhang J, Zeng XT, Lei JR, Tang YJ, Yang J. No association between XRCC1 gene Arg194Trp polymorphism and risk of lung cancer: evidence based on an updated cumulative meta-analysis. Tumour Biol. 2014;35(6):5629–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mullen B, Muellerleile P, Bryant B. Cumulative meta-analysis: a consideration of indicators of sufficiency and stability. Personal Soc Psychol Bull. 2001;27(11):1450–62.

    Article  Google Scholar 

  31. Awasthi S, Tripathi P, Ganesh S, Husain N. Association of ADAM33 gene polymorphisms with asthma in Indian children. J Hum Genet. 2011;56(3):188–95.

    Article  CAS  PubMed  Google Scholar 

  32. Qu S, Sun D, Wang Y, Zhang C, Lv Y, Yao L. Association of ADAM33 polymorphisms with childhood asthma in a northern Chinese population. Exp Mol Pathol. 2011;91(3):775–9.

    Article  CAS  PubMed  Google Scholar 

  33. Yu HC, Chen GQ, Li YQ, Wang LJ, Jiang CS, Meng LS. Association of T1 polymorphism in disintegrin and metalloprotease 33 gene with asthma. J Clin Pediatr. 2011; 29 (9):852–855 (in Chinese).

    CAS  Google Scholar 

  34. Xiong JY, He QQ, Jiang ZQ, Li JF. Association of polymorphism of T1 locus allele in ADAM33 gene with bronchial asthma. J Appl Clin Pediatr. 2009;24(16):1241–3. (Chinese).

    CAS  Google Scholar 

  35. Godava M, Kopriva F, Bohmova J, Vodicka R, Dusek L, Cvanova M, et al. Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012;156(3):236–47.

    Article  CAS  PubMed  Google Scholar 

  36. Schedel M, Depner M, Schoen C, Weiland SK, Vogelberg C, Niggemann B, et al. The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations. Respir Res. 2006;7:91.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Puxeddu I, Pang YY, Harvey A, Haitchi HM, Nicholas B, Yoshisue H, et al. The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma. J Allergy Clin Immunol. 2008;1400–1406(6):1406.e1401-1404.

    Google Scholar 

  38. Simpson A, Maniatis N, Jury F, Cakebread JA, Lowe LA, Holgate ST, et al. Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function. Am J Respir Crit Care Med. 2005;172(1):55–60.

    Article  PubMed  Google Scholar 

  39. Reijmerink NE, Kerkhof M, Koppelman GH, Gerritsen J, de Jongste JC, Smit HA, et al. Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness. Allergy. 2009;64(6):898–904.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang Y, Zhang J, Huang J, Li X, He C, Tian C, et al. Polymorphisms in the transforming growth factor-beta1 gene and the risk of asthma: a meta-analysis. Respirology. 2010;15(4):643–50.

    Article  PubMed  Google Scholar 

  41. Wang X, Li W, Huang K, Kang X, Li Z, Yang C, et al. Genetic variants in ADAM33 are associated with airway inflammation and lung function in COPD. BMC Pulm Med. 2014;14:173.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tripathi P, Awasthi S, Gao P. ADAM metallopeptidase domain 33 (ADAM33): a promising target for asthma. Mediat Inflamm. 2014;2014:572025.

    Article  Google Scholar 

  43. Bukvic BK, Blekic M, Simpson A, Marinho S, Curtin JA, Hankinson J, et al. Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure. Pediatr Allergy Immunol. 2013;24(1):10–8.

    Article  PubMed  Google Scholar 

  44. Chiang CH, Lin MW, Chung MY, Yang UC. The association between the IL-4, ADRβ2 and ADAM 33 gene polymorphisms and asthma in the Taiwanese population. J Chin Med Assoc. 2012;75(12):635–43.

    Article  CAS  PubMed  Google Scholar 

  45. Zheng XY, Guan WJ, Mao C, Chen HF, Ding H, Zheng JP, et al. Interleukin-10 promoter 1082/-819/-592 polymorphisms are associated with asthma susceptibility in Asians and atopic asthma: a meta-analysis. Lung. 2014;192(1):65–73.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Xiaoyun Zhong.

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Deng, R., Zhao, F. & Zhong, X. T1 polymorphism in a disintegrin and metalloproteinase 33 (ADAM33) gene may contribute to the risk of childhood asthma in Asians. Inflamm. Res. 66, 413–424 (2017). https://doi.org/10.1007/s00011-017-1024-8

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  • DOI: https://doi.org/10.1007/s00011-017-1024-8

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