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The Health Outcome
Asthma is characterized by inflammation in the airways that restrict a person's ability to breathe. Generally this obstruction is temporary, but in some cases medical intervention is required to alleviate the problem. Asthma can be triggered by mold, pollen, dust mites, smoke, viruses, strenuous activity, and many other risk factors. Approximately 1 in 15 Americans suffer from asthma and it is the most common chronic condition amongst children (2). About 2 million emergency room visits each year can be attributed to asthma. Every year asthma accounts for about 2 million emergency room visits, 5000 deaths, and an additional 7000 deaths are linked to this disease. (3)
Models in mice suggest that functional gene variants of the prostanoid DP receptor (PTGDR) are required for the expression of asthma. Matsuoka showed mice that do not have a functional prostanoid DP receptor were not able to express asthma (5). This paper examines the risk of asthma due to functional variants of PTGDR polymorphism in a case control setting.
The Finding
The study consisted of two populations, one white and one black. In the white population there were 518 cases of asthma and 175 controls; in the black population there were 80 cases of asthma and 45 controls. Cases were classified according to the definition of asthma set forth by the American Thoracic Society. The controls were selected from the military and had no history of asthma, atopy, or serious medical conditions. 25 random cases and controls were screened to detect variants of PTGDR with a frequency of 5% or greater. Four variants were reported to have met this specification (T-549C, C-441T, T-197C, G+1044A). An additional two variants with frequencies less than 1% were ignored in the analysis (1).
Combinations of the three promoter region variants were used to define five three-SNP haplotypes, of which four of the haplotypes had a frequency greater than 5%. These four haplotypes, CCT, TTT, TCT, and CCC, were associated with different transcription factor binding affinities. The CCC haplotype had the highest transcription efficiency while the TCT had the lowest. When adjusted for age and sex, individuals in both the white and the black populations who had at least one copy of the TCT haplotype were less likely to have asthma (Whites: Odds ratio, 0.55; 95% CI 0.38 to 0.80; P=0.002, Blacks: Odds ratio, 0.32; 95% CI 0.12 to 0.89; P=0.03). Approaching statistical significance, whites who had at least one copy of the CCC haplotype were more likely to have asthma (Odds ratio, 1.53; 95% CI 0.95 to 2.47; P=0.08).
The authors did not report an adjusted OR for blacks with at least one copy of the CCC haploytpe, but given the data from the paper a crude OR can be calculated (Odds ratio, 2.04; 95% CI 0.75-5.50; P=0.25) (1). Although the crude analysis in the black population is not significant, there appears to be a trend showing the CCC haplotype is associated with a higher risk of asthma.
The authors concluded that particular variants of PTGDR could both decrease and increase a person's risk for asthma. Their findings were supported both statistically and with biological plausibility.
Public Health Implications The main source of bias in this study comes from the choice of recruiting controls from the U.S. Army. The authors suggested that large scale, population based studies are required to further explore variants of PTGDR and the risks of asthma. The authors acknowledged that variants of PTGDR are just one of many genetic risk factors for asthma, and that further research is required to understand how these genes interact together and with environmental factors to affect asthma. Current estimates, based on preliminary screening of the human genome, suggest there may be 10 genes that contribute to asthma (4). If the results from this study are reproducible, then it is conceivable that genetic screening for variants of PTGDR , in addition to other genes, could be performed to assess the risk of an individual to develop asthma.
More relevant implications of this study include possibly accounting for the variability in patients treated with the prostanoid DP receptor antagonists through the action of the PTGDR haplotype on receptor expression. Additionally, the PTGDR variants could be used to help classify asthma cases that do not clearly express IgE-related phenotype (1).
References
- Oguma T, Palmer LJ, Birben E, Sonna LA, Asano K, Lilly CM. Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med. 2004;351:1752-1763.
- Asthmas and Allergy Foundation of America. What is Asthma? (http://www.aafa.org/display.cfm?id=8&cont=5)
(last accessed 2/2008) - Asthmas and Allergy Foundation of America. Asthma Facts and Figures.
(http://www.aafa.org/display.cfm?id=8&sub=42)
(last accessed 2/2008) - Cookson, W., et al. Making Sense of Asthma Genes. N Engl J Med. 2004; 351:1794-1796
- Matsuoka T, Hirata M, Tanaka H, et al. Prostaglandin D2 as a mediator of allergic asthma. Science 2000;287:2013-2017.
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