Abstract
The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively. Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (−731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses supported the ones of the single SNP analyses. Thus, we demonstrated significant evidence of association between polymorphisms in PTGDR with asthma phenotypes in the two Caucasian populations.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Wills-Karp M, Ewart SL . Time to draw breath: asthma-susceptibility genes are identified. Nat Rev Genet 2004; 5: 376–387.
Hardy CC, Robinson C, Tattersfield AE, Hoglgate ST . The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med 1984; 311: 209–213.
Wenzel SE, Westcott JY, Smith HR, Larsen GL . Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups. Am Rev Respir Dis 1989; 139: 450–457.
Boie Y, Sawyer N, Slipetz DM, Metters KM, Abramovitz M . Molecular cloning and characterization of the human prostanoid DP receptor. J Biol Chem 1995; 270: 18910–18916.
Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K et al. Prostaglandin D2 as a mediator of allergic asthma. Science 2000; 287: 2013–2017.
Daniels SE, Bhattacharrya S, James A, Leaves NI, Young A, Hill MR et al. A genome-wide search for quantitative trait loci underlying asthma. Nature 1996; 383: 247–250.
Malerba G, Patuzzo C, Trabetti E, Lauciello M, Galavotti R . Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic asthmatic families. J Allergy Clin Immunol 2001; 107: 654–658.
Mansur AH, Bishop DT, Markham AF, Morton NE, Holgate ST, Morrison JF . Suggestive evidence for genetic linkage between IgE phenotypes and chromosome 14q markers. Am J Respir Crit Care Med 1999; 159: 1796–1802.
Hakonarson H, Bjornsdottir US, Halapi E, Palsson S, Adalsteinsdottir E, Gislason D et al. A major susceptibility gene for asthma maps to chromosome 14q24. Am J Hum Genet 2002; 71: 483–491.
Oguma T, Palmer LJ, Birben E, Sonna A, Asano K, Lilly CM . Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med 2004; 351: 1752–1763.
Sanz C, Isidoro-Garcia M, Davila I, Moreno E, Laffond E, Avila C et al. Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma. Allergy 2006; 61: 543–548.
Noguchi E, Shibasaki M, Kamioka M, Yokouchi Y, Yamakawa-Kobayashi K, Hamaguchi H et al. New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes. Clin Exp Allergy 2002; 32: 93–96.
Tsai YJ, Choudhry S, Kho J, Beckman K, Tsai HJ, Navarro D et al. The PTGDR gene is not associated with asthma in 3 ethnically diverse populations. J Allergy Clin Immunol 2006; 118: 1242–1248.
Silverman EK, Palmer LJ . Case–control association studies for the genetics of complex respiratory diseases. Am J Respir Cell Mol Biol 2000; 22: 645–648.
Ober C . Perspectives on the past decade of asthma genetics. J Allergy Clin Immunol 2005; 116: 274–278.
Ober C, Hoffjan S . Asthma genetics 2006: the long and winding road to gene discovery. Genes Immunity 2006; 7: 95–100.
Pillai SG, Cousens DJ, Barnes AA, Buckley PT, Chiano MN, Hosking LK et al. A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma. Pharmacogenetics 2004; 14: 627–633.
Pillai SG, Chiano MN, White NJ, Speer M, Barnes KC, Carlsen K et al. A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p. Eur J Hum Genet 2006; 14: 307–316.
Barnes KC, Freidhoff LR, Horowitz EM, Mathias RA, Mulkern DM, Bonacum JT et al. Physician-derived asthma diagnoses made on the basis of questionnaire data are in good agreement with interview-based diagnoses and are not affected by objective tests. J Allergy Clin Immunol 1999; 104: 791–796.
Roses AD, Burns DK, Chissoe S, Middleton L, St Jean P . Disease-specific target selection: a critical first step down the right road. Drug Discov Today 2005; 10: 177–189.
O'Connell JR, Weeks DE . PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.
Horvath S, Xu X, Laird NM . The family based association test method: strategies for studying general genotype-phenotype associations. Eur J Hum Genet 2001; 9: 301–306.
Horvath S, Xu X, Lake SL, Silverman EK, Weiss ST, Laird NM . Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics. Genet Epidemiol 2004; 26: 61–69.
Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B et al. The structure of haplotype blocks in the human genome. Science 2002; 296: 2225–2229.
Lange C, DeMeo D, Silverman EK, Weiss ST, Laird NM . PBAT: tools for family-based association studies. Am J Hum Genet 2004; 74: 367–369.
Acknowledgements
We gratefully acknowledge the sample management and custom genotyping groups at GlaxoSmithKline.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, G., Vestbo, J., Lenney, W. et al. Association of PTGDR gene polymorphisms with asthma in two Caucasian populations. Genes Immun 8, 398–403 (2007). https://doi.org/10.1038/sj.gene.6364399
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6364399
Keywords
This article is cited by
-
The differential functional coupling of phosphodiesterase 4 to human DP and EP2 prostanoid receptors stimulated with PGD2 or PGE2
Pharmacological Reports (2021)
-
An inosine 5′-monophosphate dehydrogenase 2 single-nucleotide polymorphism impairs the effect of mycophenolic acid
The Pharmacogenomics Journal (2010)
-
Polymorphisms in the endothelin-1 (EDN1) are associated with asthma in two populations
Genes & Immunity (2008)
-
Interleukin 18 receptor 1 gene polymorphisms are associated with asthma
European Journal of Human Genetics (2008)