Correspondence

Prostanoid DP Receptor Variants and Asthma

N Engl J Med 2005; 352:837-838February 24, 2005

Article

To the Editor:

Oguma et al. (Oct. 21 issue)1 clearly demonstrate the significant association between functional genetic variants of the prostanoid DP receptor gene (PTGDR) and susceptibility to asthma. Although the authors report that there was no correlation between genotypes and total plasma IgE levels, it was not fully mentioned whether these genotypes (or diplotypes) were related to the severity and clinical parameters of asthma (e.g., the forced expiratory volume in one second and peak expiratory flow rate). The identification of genetic variants regulating the susceptibility to asthma is of great value. However, in the clinical setting, genetic factors predicting the severity of asthma might be more helpful for making decisions regarding therapeutic strategy. We would appreciate it if the authors would show the correlation between the variants of PTGDR and the severity of asthma. For the genetic diagnosis of asthma, the combinations of genetic polymorphisms are thought to be informative.2 To improve the relevance of the information, we should recognize which genetic polymorphism is associated with which aspect of clinical phenotypes.

Hiroyuki Morita, M.D., Ph.D.
Ryozo Nagai, M.D., Ph.D.
University of Tokyo, Tokyo 113-8655, Japan
hmrt-tky@umin.ac.jp

2 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   Cookson W, Moffatt M. Making sense of asthma genes. N Engl J Med 2004;351:1794-1796
   Full Text | Web of Science | Medline

To the Editor:

In their editorial accompanying the article by Oguma et al., Cookson and Moffatt (Oct. 21 issue)1 express enthusiasm for evidence that polymorphisms in the β₂-adrenergic receptor may modify the response to inhaled beta-agonists in patients with asthma. However, they wrongly cite a study by the Asthma Clinical Research Network.2 In that study, Lemanske and colleagues examined the question of whether additional salmeterol would permit a reduction in the inhaled corticosteroid dose or its elimination in patients with moderate asthma, but they did not report information on genetic modification of the response to beta-agonists. However, in a retrospective study, the Asthma Clinical Research Network did report that in comparison with persons who were homozygous for alleles encoding glycine at the 16th amino acid of the β₂-adrenergic receptor, those who were homozygous for arginine had attenuated lung-function responses to regular use of albuterol.3 These investigators have confirmed these observations in a recent prospective study.4 Therefore, it appears likely that genetic variation at this locus modifies the response to inhaled beta-agonists. The degree to which this effect is clinically important and the appropriate role for genetic “tailoring” of asthma therapy are still being determined.

Aaron Deykin, M.D.
Brigham and Women's Hospital, Boston, MA 02115
adeykin@partners.org

4 References

1. 1

   Cookson W, Moffatt M. Making sense of asthma genes. N Engl J Med 2004;351:1794-1796
   Full Text | Web of Science | Medline

2. 2

   Lemanske RF Jr, Sorkness CA, Mauger EA, et al. Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial. JAMA 2001;285:2594-2603
   CrossRef | Web of Science | Medline

3. 3

   Israel E, Drazen JM, Liggett SB, et al. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med 2000;162:75-80
   Web of Science | Medline

4. 4

   Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004;364:1505-1512
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with the correspondents that understanding the predictive power of PTGDR variants with respect to the severity of asthma is an important area of study. Our study of the role of DP receptor variants in asthma was designed to determine whether genetic differences predict susceptibility to disease. To avoid confounding by misclassification, we studied patients with well-established asthma; most cases were of moderate severity. These populations exhibited only a narrow variance in lung function and disease severity and were therefore not a suitable study population for analysis of an association between PTGDR variants and the severity of asthma. Our findings suggest that a study designed to assess the predictive power of PTGDR variants with respect to the severity of asthma and lung function in an asthmatic population with a wide spectrum of disease severity would be of interest. Like the correspondents, we are hopeful that adequately controlled, genetically stratified clinical trials will demonstrate that the PTGDR genotype in the individual patient will be a useful guide to therapy.

Craig M. Lilly, M.D.
Brigham and Women's Hospital, Boston, MA 02115
clilly@partners.org

Lyle J. Palmer, Ph.D.
University of Western Australia Centre for Medical Research, Nedlands 6009, Australia

Citing Articles (1)

Citing Articles

1. 1

   C. Sanz, M. Isidoro-Garcia, I. Davila, E. Moreno, E. Laffond, C. Avila, F. Lorente. (2006) Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma. Allergy 61:5, 543-548
   CrossRef