Pharmacogenomics of Asthma
|
Therapies typically used to treat asthma include bronchodilators such as beta-adrenergics, methylxanthines, and anti-cholinergics, as well as anti-inflammatory drugs such as corticosteroids, non-steroidal anti-inflammatory agents, and leukotriene modifiers. Responses to therapies are often highly variable. Although variations in treatment responses are likely to arise in part from environmental factors, it is thought that up to 60-80% of this variability may be due to
|
 |
| genetic factors (1). Investigation into disease pathways has allowed for a more thorough understanding of the mechanisms of drug action and identification of genes likely to be involved in treatment response. Some examples of genes of potential interest in pharmacogenomics are listed in Table 1. To read more about pharmacogenomics and public health, read the Public Health Perspective on Pharmacogenomics.
β 2 -adrenoceptor and effector pathway |
β 2AR (109690) |
5q31.32 |
16 (Arg-->Gly) |
Certain forms of severe asthma & decreased response to β2-agonists. |
27 (Gln-->Glu) |
Reduced bronchial responsiveness & elevated IgE levels in asthmatics. |
34 (Val-->Met) |
No identified change in function. |
164 (Thr-->Ile) |
Potentially decreased response to β2-agonists. |
Leukotriene synthesis |
ALOX5 (152390) |
10q11.12 |
Number of tandem Sp-1 and Egr-1 binding sites in promoter region. |
Decreased response to the antileukotriene ABT-761. |
LTC4S (246530) |
5q35 |
–-444 A-->C |
Increased risk of aspirin-induced asthma. |
*Click on the gene name for descriptive information about the gene, provided by the LocusLink database (2), and on the associated number for information about studies examining the gene, provided by the Online Mendelian Inheritance in Man (OMIM) database (3).
- Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull 2000;56:1054-70.
- LocusLink. The NCBI handbook [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2002 Oct. Chapter 17, The Reference Sequence (RefSeq) Project. World Wide Web URL: http://www.ncbi.nlm.nih.gov/LocusLink/
- Online Mendelian Inheritance in Man, OMIM (TM). McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 2000.
World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/
|
|
|