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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

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Abstract

Introduction

Asthma is one of the most common chronic diseases in children. It is caused by complex interactions between various genetic factors and exposures to environmental allergens and irritants. Because of the heterogeneity of the disease and the genetic and cultural differences among different populations, a proper association study and genetic testing for asthma and susceptibility genes is difficult to perform.

Materials and Methods

We assessed 13 single-nucleotide polymorphisms (SNPs) in seven well-known asthma susceptibility genes and looked for association with pediatric asthma using 449 asthmatic subjects and 512 non-asthma subjects in Taiwanese population.

Results

CD14-159 C/T and MS4A2 Glu237Gly were identified to have difference in genotype/allele frequencies between the control group and asthma patients. Moreover, the genotype synergistic analysis showed that the co-contribution of two functional SNPs was riskier or more protective from asthma attack. Our study provided a genotype synergistic method for studying gene–gene interaction on polymorphism basis and genetic testing using multiple polymorphisms.

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References

  1. Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of GINA Dissemination Committee Report. Allergy. 2004;59:469–78. doi:10.1111/j.1398-9995.2004.00526.x.

    Article  PubMed  Google Scholar 

  2. Burr ML, Butland BK, King S, Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child. 1989;64:1452–6.

    Article  PubMed  CAS  Google Scholar 

  3. Beasley R. The burden of asthma with specific reference to the United States. J Allergy Clin Immunol. 2002;109:S482–9. doi:10.1067/mai.2002.122716.

    Article  PubMed  Google Scholar 

  4. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347:911–20. doi:10.1056/NEJMra020100.

    Article  PubMed  Google Scholar 

  5. Skadhauge LR, Christensen K, Kyvik KO, Sigsgaard T. Genetic and environmental influence on asthma: a population-based study of 11688 Danish twin pairs. Eur Respir J. 1999;13:8–14. doi:10.1183/09031936.99.13100899.

    Article  PubMed  CAS  Google Scholar 

  6. Palmer LJ, Burton PR, James AL, Musk AW, Cookson WO. Familiar aggregation and heritability of asthma-associated quantitative traits in a population-base sample of nuclear families. Eur J Hum Genet. 2000;8:853–60. doi:10.1038/sj.ejhg.5200551.

    Article  PubMed  CAS  Google Scholar 

  7. Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun. 2006;7:95–100. doi:10.1038/sj.gene.6364284.

    Article  PubMed  CAS  Google Scholar 

  8. Holloway JW, Beghe B, Holgate ST. The genetic basis of atopic asthma. Clin Exp Allergy. 1999;29:1023–32. doi:10.1046/j.1365-2222.1999.00599.x.

    Article  PubMed  CAS  Google Scholar 

  9. Anderson GG, Cookson WO. Recent advanced in the genetics of allergy and asthma. Mol Med Today. 1999;5:264–73. doi:10.1016/S1357-4310(99)01479-3.

    Article  PubMed  CAS  Google Scholar 

  10. Blumenthal MM. What we know about the genetics of asthma at the beginning of the 21st century. Clin Rev Allergy Immunol. 2002;22:11–31.

    Article  PubMed  CAS  Google Scholar 

  11. Huang JL. Asthma severity and genetics in Taiwan. J Microbiol Immunol Infect. 2005;38:158–63.

    PubMed  CAS  Google Scholar 

  12. Burney PG, Luczynska C, Chinn S, Jarvis D. The European Community Respiratory Health Survey. Eur Respir J. 1994;5:954–60.

    Google Scholar 

  13. Pearce N, Sunyer J, Cheng S, Chinn S, Bjorksten B, Burr M, Keil U, Anderson HR, Burney P. Comparison of asthma prevalence in the ISAAC and the ECRHS. ISAAC Steering Committee and the European Community Respiratory Health Survey. International Study of Asthma and Allergies in Childhood. Eur Respir J. 2000;16:420–6. doi:10.1183/9031936.00.16337700.

    Article  PubMed  CAS  Google Scholar 

  14. Beydon N, Davis SD, Lombardi E, Allen JL, Arets HGM, Aurora P, Bisgaard H, Davis GM, Ducharme FM, Eigen H, Gappa M, Gaultier C, Gustafsson PM, Hall GL, Hantos Z, Healy MJR, Jones MH, Klug B, Carlsen KCL, McKenzie SA, Marchal F, Mayer OH, Merkus PJFM, Morris MG, Oostveen E, Pillow JJ, Seddon PC, Silverman M, Sly PD, Stocks J, Tepper RS, Vilozni D, Wilson NH, behalf of the American Thoracic Society/European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing. An official American Thoracic Society/European Respiratory Society Statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007;175:1304–45. doi:10.1164/rccm.200605-642ST.

    Article  PubMed  Google Scholar 

  15. Wang JY. The study of bronchial hyperactivity of asthmatic children by forced oscillation method. Asian Pac J Allergy Immunol. 1991;9:51–6.

    PubMed  CAS  Google Scholar 

  16. Leung TF, Tang NLS, Chan HIS, Li AM, Ha G, Lam CWK, Fok TF. Distribution in allele frequencies of predisposition-to atopy genotypes in Chinese children. Pediatr Pulmonol. 2002;34:419–24. doi:10.1002/ppul.10210.

    Article  PubMed  CAS  Google Scholar 

  17. Unoki M, Furuta S, Onouchi Y, Watanabe O, Doi S, Fujiwara H, Miyatake A, Fujita K, Tamari M, Nakamura Y. Association studies of 33 single nucleotide polymorphisms (SNPs) in 29 candidate genes for bronchial asthma: positive association a T294C polymorphism in the thromboxane A2 receptor gene. Hum Genet. 2000;106:440–6. doi:10.1007/s004390000267.

    Article  PubMed  CAS  Google Scholar 

  18. Harkonarson H, Bjornsdottir US, Ostermann E, Arnason T, Adalsteinsdottir AE, Halapi E, Shkolny D, Kristjansson K, Gidnadottir SA, Frigge ML, Gislason D, Gislason T, Kong A, Gulcher J, Stefansson K. Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland. Am J Respir Crit Care Med. 2001;164:2036–44.

    Google Scholar 

  19. Savage SA. Genetic association studies: where are we now. Person Med. 2006;3:371–4. doi:10.2217/17410541.3.4.371.

    Article  Google Scholar 

  20. Baldini M, Lohman IC, Halonen M, Erickson RP, Holt P, Martinez FD. A polymorphism in the 5′-flanking region of the CD14 gene in associated with circulating soluble CD14 levels and with total serum IgE. Am J Respir Cell Mol Biol. 1999;20:976–83.

    PubMed  CAS  Google Scholar 

  21. Tan CY, Chen YL, Wu LSH, Liu CF, Chang WT, Wang JY. Association of CD14 promoter polymorphisms and soluble CD14 levels in mite allergen sensitization of children in Taiwan. J Hum Genet. 2006;51:59–67. doi:10.1007/s10038-005-0323-z.

    Article  PubMed  CAS  Google Scholar 

  22. Martinez FD. CD14, endotoxin, and asthma risk. Proc Am Thorac Soc. 2007;4:221–5. doi:10.1513/pats.200702-035AW.

    Article  PubMed  CAS  Google Scholar 

  23. Wang JY, Wang LM, Lin CGJ, Chang ACW, Wu LSH. Association study using combination analysis of SNP and STRP markers: CD14 promoter polymorphism and IgE level in Taiwanese asthma children. J Hum Genet. 2005;50:36–41. doi:10.1007/s10038-004-0215-7.

    Article  PubMed  CAS  Google Scholar 

  24. Chou TY, Wu KY, Shieh CC, Wang JY. The clinical efficacy of in vitro allergen-specific IgE antibody test in the diagnosis of allergic children with asthma. Acta Paediatr Taiwan. 2002;43:35–9.

    PubMed  Google Scholar 

  25. Wu JY, Shyur SD, Huang LH, Weng JD, Chuo HT, Ma YC, Lin SC, Wu WC. Symptom scores, pulmonary unction tests and levels of allergen specific IgE in asthmatic children. The Official Bulletin of the Society of Pediatric Pulmonology, Taiwan. ROC. 2003;4:1–7.

    Google Scholar 

  26. Hill MR, Cookson WOCM. A new variant of the beta subunit of the high-affinity receptor for immunoglobulin E (Fc-epsilon-RI-beta E237G): associations with measures of atopy and bronchial hyper-responsiveness. Hum Mol Genet. 1996;5:959–62. doi:10.1093/hmg/5.7.959.

    Article  PubMed  CAS  Google Scholar 

  27. Shirakawa T, Mao XQ, Sasaki S, Enomoto T, Kawai M, Morimoto K, Hopkin J. Association between atopic asthma and a coding variant of Fc-epsilon-RI-beta in a Japanese population. Hum Mol Genet. 1996;5:1129–30. doi:10.1093/hmg/5.8.1129.

    Article  PubMed  CAS  Google Scholar 

  28. Finkelman FD, Vervelli D. Advances in asthma, allergy mechanisms, and genetics in 2006. J Allergy Clin Immunol. 2007;120:544–50. doi:10.1016/j.jaci.2007.05.025.

    Article  PubMed  CAS  Google Scholar 

  29. Vercelli D. Genetics, epigenetics, and the environment: switching, buffering, releasing. J Allergy Clin Immunol. 2004;113:381–6. doi:10.1016/j.jaci.2004.01.752.

    Article  PubMed  CAS  Google Scholar 

  30. Howard TD, Koppelman GH, Xu J, Zheng SL, Postma DS, Meyers DA, Bleecker ER. Gene–gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Am J Hum Genet. 2002;70:230–6. doi:10.1086/338242.

    Article  PubMed  CAS  Google Scholar 

  31. Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R. Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol. 2004;113:489–95. doi:10.1016/j.jaci.2003.12.037.

    Article  PubMed  CAS  Google Scholar 

  32. Chan IH, Leung TF, Tang NL, Li CY, Sung YM, Wong GW, Wong CK, Lam CW. Gene–gene interactions for asthma and plasma total IgE concentration in Chinese children. J Allergy Clin Immunol. 2006;117:127–33. doi:10.1016/j.jaci.2005.09.031.

    Article  PubMed  CAS  Google Scholar 

  33. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, von Mutius E. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol. 2006;117:269–74. doi:10.1016/j.jaci.2005.10.024.

    Article  PubMed  CAS  Google Scholar 

  34. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008;8:169–82. doi:10.1038/nri2257.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics and Institute of Molecular Medicine, College of Medicine, National Cheng-Kung University, Tainan, Taiwan

    Jiu-Yao Wang

  2. Research and Product Development Division, Vita Genomics Inc., 7Fl., No.6, Sec.1, Jungshing Rd., Wugu Shiang, Taipei County, 248, Taiwan

    Ya-Huei Liou, Ying-Jye Wu, Ya-Hsin Hsiao & Lawrence Shih-Hsin Wu

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  1. Jiu-Yao Wang
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  2. Ya-Huei Liou
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  5. Lawrence Shih-Hsin Wu
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Correspondence to Lawrence Shih-Hsin Wu.

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ESM Supplement Table 1

The highest frequencies two subgroups of total nine subgroups and the results for comparing to sum of other subgroups by χ 2 test (DOC 361 KB)

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Wang, JY., Liou, YH., Wu, YJ. et al. 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. J Clin Immunol 29, 205–209 (2009). https://doi.org/10.1007/s10875-008-9256-6

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  • DOI: https://doi.org/10.1007/s10875-008-9256-6

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