Advertisement

Molecular Biology Reports

, Volume 40, Issue 3, pp 2195–2203 | Cite as

PTGDR polymorphisms and susceptibility to asthma: a meta-analysis

  • Young Ho Lee
  • Sung Jae Choi
  • Jong Dae Ji
  • Gwan Gyu Song
Article

Abstract

The aim of this study was to explore whether prostaglandin D2 receptor (PTGDR) polymorphisms confer susceptibility to asthma. A meta-analysis was conducted on the associations between the PTGDR −549 C/T, −441 C/T, and −197 C/T polymorphisms and asthma using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. Three polymorphism haplotypes were constructed in the order −549/−441/−179. Meta-analysis was performed on the haplotype CCC (high transcriptional activity) and of TCT (low transcriptional activity). A total of 13 separate comparative studies in 9 articles involving 7,155 patients with asthma and 7,285 control subjects were included in this meta-analysis. An association between asthma and the PTGDR −549 C/T polymorphism was found by allele contrast (OR = 1.133, 95 % CI = 1.004–1.279, P = 0.043). Ethnicity-specific meta-analysis showed an association between asthma and the PTGDR −549 C allele in Europeans (OR = 1.192, 95 % CI = 1.032–1.377, P = 0.017). Furthermore, stratifying subjects by age indicated an association between the PTGDR −549 C allele and asthma in adults (OR = 1.248, 95 % CI = 1.076–1.447, P = 0.003), but no association in children (OR = 0.933, 95 % CI = 0.756–1.154, P = 0.324). Analyses using the dominant and additive models showed the similar pattern as that observed for the PTGDR −549 C allele, that is, a significant association in Europeans and adults, but not in children. No association was found between asthma and the PTGDR −441 C/T or −197 C/T polymorphisms, and meta-analysis stratified by ethnicity and age also revealed no association between asthma and these polymorphisms. Furthermore, no association was found between asthma and the CCC and TCT haplotypes of PTGDR, and meta-analysis stratified by ethnicity and age revealed no association between asthma and the CCC and TCT PTGDR haplotypes. This meta-analysis demonstrates that the PTGDR −549 C/T polymorphism confers susceptibility to asthma in Europeans and adults. However, no association was found between the PTGDR 441 C/T and −197 C/T polymorphisms or the CCC and TCT haplotypes and asthma susceptibility.

Keywords

Asthma Prostaglandin D2 receptor Polymorphism Meta-analysis 

Notes

Acknowledgments

This study was supported by a Korea University Grant.

Conflict of interest

The authors have no financial or non-financial conflict of interest to declare.

References

  1. 1.
    Bousquet J, Clark TJ, Hurd S, Khaltaev N, Lenfant C, O’byrne P, Sheffer A (2007) GINA guidelines on asthma and beyond. Allergy 62:102–112PubMedGoogle Scholar
  2. 2.
    Li X, Howard TD, Zheng SL, Haselkorn T, Peters SP, Meyers DA, Bleecker ER (2010) Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J Allergy Clin Immunol 125(2):328–335PubMedCrossRefGoogle Scholar
  3. 3.
    Liu MC, Bleecker ER, Lichtenstein LM, Kagey-Sobotka A, Niv Y, McLemore TL, Permutt S, Proud D, Hubbard WC (1990) Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma. Am Rev Respir Dis 142:126–132PubMedGoogle Scholar
  4. 4.
    Liu MC, Hubbard WC, Proud D, Stealey BA, Galli SJ, Kagey-Sobotka A, Bleecker ER, Lichtenstein LM (1991) Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics. Cellular, mediator, and permeability changes. Am Rev Respir Dis 144:51–58PubMedCrossRefGoogle Scholar
  5. 5.
    Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y, Eguchi N, Urade Y, Yoshida N, Kimura K, Mizoguchi A, Honda Y, Nagai H, Narumiya S (2000) Prostaglandin D2 as a mediator of allergic asthma. Science 287:2013–2017PubMedCrossRefGoogle Scholar
  6. 6.
    Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K (2001) Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193:255–261PubMedCrossRefGoogle Scholar
  7. 7.
    Oguma T, Palmer LJ, Birben E, Sonna LA, Asano K, Lilly CM (2004) Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med 351:1752–1763PubMedCrossRefGoogle Scholar
  8. 8.
    Birbian N, Singh J, Jindal SK, Joshi A, Batra N (2011) No association of PTGDR -441C/T polymorphism with asthma in a North Indian population. Dis Markers 31(6):353–359PubMedGoogle Scholar
  9. 9.
    Isidoro-Garcia M, Sanz C, Garcia-Solaesa V, Pascual M, Pescador DB, Lorente F, Davila I (2011) PTGDR gene in asthma: a functional, genetic, and epigenetic study. Allergy 66(12):1553–1562PubMedCrossRefGoogle Scholar
  10. 10.
    Kang MJ, Kwon JW, Kim BJ, Yu J, Choi WA, Shin YJ, Hong SJ (2011) Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma. J Hum Genet 56(4):284–289PubMedCrossRefGoogle Scholar
  11. 11.
    Jamrozik EF, Warrington N, McClenaghan J, Hui J, Musk AW, James A, Beilby JP, Hansen J, De Klerk NH, Palmer LJ (2011) Functional haplotypes in the PTGDR gene fail to associate with asthma in two Australian populations. Respirology 16(2):359–366PubMedCrossRefGoogle Scholar
  12. 12.
    Blakey JD, Sayers I, Ring SM, Strachan DP, Hall IP (2009) Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 birth cohort. Thorax 64:381–387PubMedCrossRefGoogle Scholar
  13. 13.
    Leung TF, Li CY, Kong AP, Chan IH, Ng MC, Chan MH, So WY, Wong GW, Lam CW, Chan JC (2009) PTGDR is not a major candidate gene for asthma and atopy in Chinese children. Pediatr Allergy Immunol 20:556–562PubMedCrossRefGoogle Scholar
  14. 14.
    Sanz C, Isidoro-Garcia M, Davila I, de Pedro MP, Mendez Sde A, Padron J, Ruiz-SanFrancisco A, Lorente F (2009) A new PTGDR promoter polymorphism in a population of children with asthma. Pediatr Allergy Immunol 20:151–156PubMedCrossRefGoogle Scholar
  15. 15.
    Li J, Liu Q, Wang P, Li H, Wei C, Guo C, Gong Y (2007) Lack of association between three promoter polymorphisms of PTGDR gene and asthma in a Chinese Han population. Int J Immunogenet 34:353–357PubMedCrossRefGoogle Scholar
  16. 16.
    Tsai YJ, Choudhry S, Kho J, Beckman K, Tsai HJ, Navarro D, Matallana H, Castro RA, Lilly CM, Nazario S, Rodriguez-Santana JR, Casal J, Torres A, Salas J, Chapela R, Watson HG, Meade K, Avila PC, Rodriguez-Cintron W, LeNoir M, Burchard EG (2006) The PTGDR gene is not associated with asthma in 3 ethnically diverse populations. J Allergy Clin Immunol 118:1242–1248PubMedCrossRefGoogle Scholar
  17. 17.
    Sanz C, Isidoro-Garcia M, Davila I, Moreno E, Laffond E, Avila C, Lorente F (2006) Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma. Allergy 61:543–548PubMedCrossRefGoogle Scholar
  18. 18.
    Lee YH, Harley JB, Nath SK (2006) Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 14:364–371PubMedCrossRefGoogle Scholar
  19. 19.
    Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2006) Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27:157–161PubMedCrossRefGoogle Scholar
  20. 20.
    Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, Harley JB (2007) The PTPN22 C1858T functional polymorphism and autoimmune diseases–a meta-analysis. Rheumatology (Oxford) 46:49–56CrossRefGoogle Scholar
  21. 21.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  22. 22.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  23. 23.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  24. 24.
    Arima M, Fukuda T (2011) Prostaglandin D and T(H)2 inflammation in the pathogenesis of bronchial asthma. Korean J Intern Med 26:8–18PubMedCrossRefGoogle Scholar
  25. 25.
    Hardy CC, Robinson C, Tattersfield AE, Holgate ST (1984) The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med 311:209–213PubMedCrossRefGoogle Scholar
  26. 26.
    Wenzel SE, Westcott JY, Smith HR, Larsen GL (1989) Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups. An alteration in the ratio of bronchoconstrictive to bronchoprotective mediators. Am Rev Respir Dis 139:450–457PubMedCrossRefGoogle Scholar
  27. 27.
    Malerba G, Patuzzo C, Trabetti E, Lauciello MC, Galavotti R, Pescollderungg L, Whalen MB, Zanoni G, Martinati LC, Boner AL, Pignatti PF (2001) Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic asthmatic families. J Allergy Clin Immunol 107:654–658PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Young Ho Lee
    • 1
  • Sung Jae Choi
    • 1
  • Jong Dae Ji
    • 1
  • Gwan Gyu Song
    • 1
  1. 1.Division of Rheumatology, Department of Internal MedicineKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea

Personalised recommendations