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No Association Between −159C/T Polymorphism of the CD14 Gene and Asthma Risk: a Meta-Analysis of 36 Case-Control Studies

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Abstract

Numerous studies have evaluated the association between −159C/T polymorphism of the CD14 gene and asthma risk; however, these studies have yielded inconsistent results. We performed meta-analyses to investigate the association between CD14-159C/T polymorphism and asthma risk. Studies were identified from PubMed, Embase, and two Chinese databases. Odds ratios (ORs) with 95 % confidence interval (CI) were used to evaluate the strength of association. Thirty-six studies were collected for meta-analysis, which involved 6954 cases and 7525 controls. In the overall populations, no significant association between the CD14-159C/T polymorphism and asthma risk was found for the dominant (OR = 0.90, 95 % CI = 0.81–1.01, P = 0.08) or other models; stratified analyses indicated that the CD14-159C/T polymorphism was not associated with asthma risk in Caucasians or Asians or adults or children. Among the atopic asthma populations, no significant results were observed in the all-combined or subgroup analyses. This meta-analysis demonstrates that the CD14-159C/T polymorphism may not be a risk factor for asthma.

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References

  1. Zhao, L., and M.B. Bracken. 2011. Association of CD14–260 (-159) C > T and asthma: a systematic review and meta-analysis. BMC Medical Genetics 12: 93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Los, H., P.E. Postmus, and D.I. Boomsma. 2001. Asthma genetics and intermediate phenotypes: a review from twin studies. Twin Research 4(2): 81–93.

    Article  CAS  PubMed  Google Scholar 

  3. Lau, M.Y., S.C. Dharmage, J.A. Burgess, A.J. Lowe, C.J. Lodge, B. Campbell, et al. 2014. CD14 polymorphisms, microbial exposure and allergic diseases: a systematic review of gene-environment interactions. Allergy 69(11): 1440–1453.

    Article  CAS  PubMed  Google Scholar 

  4. Klaassen, E.M., B.E. Thonissen, G. van Eys, E. Dompeling, and Q. Jobsis. 2013. A systematic review of CD14 and toll-like receptors in relation to asthma in Caucasian children. Allergy, Asthma and Clinical Immunology 9(1): 10.

    Article  CAS  Google Scholar 

  5. Bouzigon, E., P. Forabosco, G.H. Koppelman, W.O. Cookson, M.H. Dizier, D.L. Duffy, et al. 2010. Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy. European Journal of Human Genetics 18(6): 700–706.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Buckova, D., L.I. Holla, M. Schuller, V. Znojil, and J. Vacha. 2003. Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE-mediated allergy. Allergy 58(10): 1023–1026.

    Article  CAS  PubMed  Google Scholar 

  7. Kedda, M.A., F. Lose, D. Duffy, E. Bell, P.J. Thompson, and J. Upham. 2005. The CD14 C-159T polymorphism is not associated with asthma or asthma severity in an Australian adult population. Thorax 60(3): 211–214.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Perin, P., V. Berce, and U. Potocnik. 2011. CD14 gene polymorphism is not associated with asthma but rather with bronchial obstruction and hyperreactivity in Slovenian children with non-atopic asthma. Respiratory Medicine 105(Suppl 1): S54–S59.

    Article  PubMed  Google Scholar 

  9. Zhang, Y., C. Tian, J. Zhang, X. Li, H. Wan, C. He, et al. 2011. The -159C/T polymorphism in the CD14 gene and the risk of asthma: a meta-analysis. Immunogenetics 63(1): 23–32.

    Article  CAS  PubMed  Google Scholar 

  10. Nishimura, F., M. Shibasaki, K. Ichikawa, T. Arinami, and E. Noguchi. 2006. Failure to find an association between CD14-159C/T polymorphism and asthma: a family-based association test and meta-analysis. Allergology International 55(1): 55–58.

    Article  PubMed  Google Scholar 

  11. Wang, J., M. Simayi, Q. Wushouer, Y. Xia, Y. He, F. Yan, et al. 2014. Association between polymorphisms in ADAM33, CD14, and TLR4 with asthma in the Uygur population in China. Genetics and Molecular Research 13(2): 4680–4690.

    Article  CAS  PubMed  Google Scholar 

  12. Sahin, F., P. Yildiz, A. Kuskucu, M.A. Kuskucu, N. Karaca, and K. Midilli. 2014. The effect of CD14 and TLR4 gene polymorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study. BMC Pulmonary Medicine 14: 20.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Hussein, Y.M., S.M. Shalaby, H.E. Zidan, N.A. Sabbah, N.A. Karam, and S.S. Alzahrani. 2013. CD14 tobacco gene-environment interaction in atopic children. Cellular Immunology 285(1-2): 31–37.

    Article  CAS  PubMed  Google Scholar 

  14. Bose, P., R. Bathri, S. De, and K.K. Maudar. 2013. CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India. Indian Journal of Human Genetics 19(2): 188–195.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Yazdani, N., M.M. Amoli, M. Naraghi, A. Mersaghian, F. Firouzi, F. Sayyahpour, et al. 2012. Association between the functional polymorphism C-159T in the CD14 promoter gene and nasal polyposis: potential role in asthma. Journal of Investigational Allergology & Clinical Immunology 22(6): 406–411.

    CAS  Google Scholar 

  16. Micheal, S., K. Minhas, M. Ishaque, F. Ahmed, and A. Ahmed. 2011. Promoter polymorphisms of the CD14 gene are associated with atopy in Pakistani adults. Journal of Investigational Allergology & Clinical Immunology 21(5): 394–397.

    CAS  Google Scholar 

  17. Wu, S.Q., K.B. Zhang, H.Q. Chen, Z.G. Zhao, G.L. Wang, and C. Chen. 2011. Association between gene polymorphism of CD14-159 (C/T) and allergic asthma. Molecular Medicine Reports 4(6): 1127–1130.

    CAS  PubMed  Google Scholar 

  18. Zaborowski, T., K. Wojas-Krawczyk, P. Krawczyk, O. Jankowska, J. Siwiec, T. Kucharczyk, et al. 2011. The effect of CD14 and TLR4 gene polymorphisms on the occurrence of atopic and non-atopic asthma. Advances in Clinical and Experimental Medicine 20(4): 413–421.

    Google Scholar 

  19. Zhang, Y.N., Y.J. Li, H. Li, H. Zhou, and X.J. Shao. 2015. Association of CD14 C159T polymorphism with atopic asthma susceptibility in children from Southeastern China: a case-control study. Genetics and Molecular Research 14(2): 4311–4317.

    Article  CAS  PubMed  Google Scholar 

  20. Higgins, J.P., and S.G. Thompson. 2002. Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 21(11): 1539–1558.

    Article  PubMed  Google Scholar 

  21. Higgins, J.P., S.G. Thompson, J.J. Deeks, and D.G. Altman. 2003. Measuring inconsistency in meta-analyses. BMJ 327(7414): 557–560.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kuo Chou, T.N., Y.S. Li, K.H. Lue, C.F. Liao, C.Y. Lin, P.R. Tzeng, et al. 2010. Genetic polymorphism of manganese superoxide dismutase is associated with childhood asthma. The Journal of Asthma 47(5): 532–538.

    Article  CAS  PubMed  Google Scholar 

  23. Wu, X., Y. Li, Q. Chen, F. Chen, P. Cai, L. Wang, et al. 2010. Association and gene-gene interactions of eight common single-nucleotide polymorphisms with pediatric asthma in middle China. The Journal of Asthma 47(3): 238–244.

    Article  CAS  PubMed  Google Scholar 

  24. Bjornvold, M., M.C. Munthe-Kaas, T. Egeland, G. Joner, K. Dahl-Jorgensen, P.R. Njolstad, et al. 2009. A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma. Genes and Immunity 10(2): 181–187.

    Article  CAS  PubMed  Google Scholar 

  25. Smit, L.A., V. Siroux, E. Bouzigon, M.P. Oryszczyn, M. Lathrop, F. Demenais, et al. 2009. CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults. American Journal of Respiratory and Critical Care Medicine 179(5): 363–368.

    Article  CAS  PubMed  Google Scholar 

  26. Wang, J.Y., Y.H. Liou, Y.J. Wu, Y.H. Hsiao, and L.S. Wu. 2009. An association study of 13 SNPs from seven candidate genes with pediatric asthma and a preliminary study for genetic testing by multiple variants in Taiwanese population. Journal of Clinical Immunology 29(2): 205–209.

    Article  PubMed  Google Scholar 

  27. Kowal, K., A. Bodzenta-Lukaszyk, A. Pampuch, M. Szmitkowski, S. Zukowski, M.B. Donati, et al. 2008. Analysis of -675 4G/5G SERPINE1 and C-159T CD14 polymorphisms in house dust mite-allergic asthma patients. Journal of Investigational Allergology & Clinical Immunology 18(4): 284–292.

    CAS  Google Scholar 

  28. de Faria, I.C., E.J. de Faria, A.A. Toro, J.D. Ribeiro, and C.S. Bertuzzo. 2008. Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents. The Journal of Pediatrics 84(3): 203–210.

    Google Scholar 

  29. Lachheb, J., I.B. Dhifallah, H. Chelbi, K. Hamzaoui, and A. Hamzaoui. 2008. Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children. Tissue Antigens 71(5): 417–425.

    Article  CAS  PubMed  Google Scholar 

  30. Smit, L.A., S.I. Bongers, H.J. Ruven, G.T. Rijkers, I.M. Wouters, D. Heederik, et al. 2007. Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. Clinical and Experimental Allergy 37(11): 1602–1608.

    Article  CAS  PubMed  Google Scholar 

  31. Bernstein, D.I., N. Wang, P. Campo, R. Chakraborty, A. Smith, A. Cartier, et al. 2006. Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes. Annals of Allergy, Asthma & Immunology 97(6): 800–806.

    Article  CAS  Google Scholar 

  32. Hong, S.J., H.B. Kim, M.J. Kang, S.Y. Lee, J.H. Kim, B.S. Kim, et al. 2007. TNF-alpha (-308 G/A) and CD14 (-159T/C) polymorphisms in the bronchial responsiveness of Korean children with asthma. The Journal of Allergy and Clinical Immunology 119(2): 398–404.

    Article  CAS  PubMed  Google Scholar 

  33. Zambelli-Weiner, A., E. Ehrlich, M.L. Stockton, A.V. Grant, S. Zhang, P.N. Levett, et al. 2005. Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. The Journal of Allergy and Clinical Immunology 115(6): 1203–1209.

    Article  CAS  PubMed  Google Scholar 

  34. Sharma, M., J. Batra, U. Mabalirajan, S. Goswami, D. Ganguly, B. Lahkar, et al. 2004. Suggestive evidence of association of C-159T functional polymorphism of the CD14 gene with atopic asthma in northern and northwestern Indian populations. Immunogenetics 56(7): 544–547.

    Article  CAS  PubMed  Google Scholar 

  35. Heinzmann, A., H. Dietrich, S.P. Jerkic, T. Kurz, and K.A. Deichmann. 2003. Promoter polymorphisms of the CD14 gene are not associated with bronchial asthma in Caucasian children. European Journal of Immuno Genetics 30(5): 345–348.

    Article  CAS  Google Scholar 

  36. Woo, J.G., A. Assa’ad, A.B. Heizer, J.A. Bernstein, and G.K. Hershey. 2003. The -159 C-->T polymorphism of CD14 is associated with nonatopic asthma and food allergy. The Journal of Allergy and Clinical Immunology 112(2): 438–444.

    Article  CAS  PubMed  Google Scholar 

  37. Sengler, C., A. Haider, C. Sommerfeld, S. Lau, M. Baldini, F. Martinez, et al. 2003. Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort. Clinical and Experimental Allergy 33(2): 166–169.

    Article  CAS  PubMed  Google Scholar 

  38. Lis, G., E. Kostyk, M. Sanak, and J.J. Pietrzyk. 2001. Molecular studies in a population of children with bronchial asthma. I. Polymorphism in the promotor region of gene CD14. Pneumonologia i Alergologia Polska 69(5-6): 265–272.

    CAS  PubMed  Google Scholar 

  39. Koppelman, G.H., N.E. Reijmerink, Stine O. Colin, T.D. Howard, P.A. Whittaker, D.A. Meyers, et al. 2001. Association of a promoter polymorphism of the CD14 gene and atopy. American Journal of Respiratory and Critical Care Medicine 163(4): 965–969.

    Article  CAS  PubMed  Google Scholar 

  40. Alexis, N., M. Eldridge, W. Reed, P. Bromberg, and D.B. Peden. 2001. CD14-dependent airway neutrophil response to inhaled LPS: role of atopy. The Journal of Allergy and Clinical Immunology 107(1): 31–35.

    Article  CAS  PubMed  Google Scholar 

  41. Murk, W., K. Walsh, L.I. Hsu, L. Zhao, M.B. Bracken, and A.T. Dewan. 2011. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Human Heredity 71(2): 97–105.

    Article  PubMed  Google Scholar 

  42. Hakonarson, H., U.S. Bjornsdottir, E. Ostermann, T. Arnason, A.E. Adalsteinsdottir, E. Halapi, et al. 2001. Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland. American Journal of Respiratory and Critical Care Medicine 164(11): 2036–2044.

    Article  CAS  PubMed  Google Scholar 

  43. Chan, I.H., N.L. Tang, T.F. Leung, W. Huang, Y.Y. Lam, C.Y. Li, et al. 2008. Study of gene-gene interactions for endophenotypic quantitative traits in Chinese asthmatic children. Allergy 63(8): 1031–1039.

    Article  CAS  PubMed  Google Scholar 

  44. Park, S.O., M.Y. Jo, S.S. Jung, and G.S. Ahn. 2006. No association of polymorphisms in RANTES and CD14 genes with asthma in the Korean population. Korean Journal of Genetics 28(1): 75–81.

    CAS  Google Scholar 

  45. Cui, T.P., W.C. Jiang, and J.M. Wu. 2003. Genetic polymorphism of CD14 and allergic asthma in children. Central China Medical Journal 27(5): 235–236.

    Google Scholar 

  46. Chen, M., B. Wu, and W. Li. 2009. Influence of CD14 gene -159C/T polymorphism on IL-5 level in patients with asthma. Shang Dong Yi Yao 49(5): 13–15.

    CAS  Google Scholar 

  47. Leung, T.F., N.L. Tang, Y.M. Sung, A.M. Li, G.W. Wong, I.H. Chan, et al. 2003. The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children. Pediatric Allergy and Immunology 14(4): 255–260.

    Article  PubMed  Google Scholar 

  48. Marsh, D.G., J.D. Neely, D.R. Breazeale, B. Ghosh, L.R. Freidhoff, E. Ehrlich-Kautzky, et al. 1994. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 264(5162): 1152–1156.

    Article  CAS  PubMed  Google Scholar 

  49. Baldini, M., I.C. Lohman, M. Halonen, R.P. Erickson, P.G. Holt, and F.D. Martinez. 1999. A polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. American Journal of Respiratory Cell and Molecular Biology 20(5): 976–983.

    Article  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, China

      Rui Zhang & Hong Chen

    2. Neonatal Department, Chongqing Health Center for Women and Children, No. 64, Jintang Road, Yuzhong District, Chongqing, 400013, China

      Rui Deng

    3. Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 76, Linjiang Road, Yuzhong District, Chongqing, 400010, China

      He Li

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    Rui Zhang and Rui Deng contributed equally to this work.

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    Zhang, R., Deng, R., Li, H. et al. No Association Between −159C/T Polymorphism of the CD14 Gene and Asthma Risk: a Meta-Analysis of 36 Case-Control Studies. Inflammation 39, 457–466 (2016). https://doi.org/10.1007/s10753-015-0269-z

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