THE PHARMACOGENETICS OF ASTHMA TREATMENT

  • Chinchilli, Vernon (PI)
  • WEISS, SCOTT (PI)
  • WEISS, SCOTT (PI)
  • DRAZEN, DEBORAH (PI)
  • LANDER, ARTHUR (PI)
  • FORD, AMASA BROOKS (PI)
  • MARTIN, ALAN (PI)

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from investigator's abstract): Asthma is a chronic
inflammatory syndrome of the airways which afflicts over 12 million people in
the USA. It is characterized physiologically by recurrent airway obstruction
which resolves spontaneously or as a result of treatment, Its etiology remains
unknown. Despite the lack of understanding of is etiology, there are effective
treatment for asthma. There are three main classes of asthma treatment in use
today, inhaled B-agonists, inhaled corticosteroids and leukotriene modifiers; a
given patient may use one, two or all of these types of treatments. The
treatments are not uniformly effective; they vary in their efficacy amongst
individuals and there are compelling preliminary data (outlined herein)
suggesting that at least half of the variance in the treatment response may be
genetic in origin; our proposal is structured to identify the genes responsible
for this variable response.

Our proposed approach is straightforward. For each of the three major asthma
treatment pathways, we will: 1)Define a panel of target genes which are likely
to modify the function of the pathway; 2) Scan these targets for DNA sequence
variants; 3) As variants are identified they will ascertain which, if any,
alter either the level of expression of function of their encoded proteins; 4)
Genotype, at loci associated with functional implications in vitro, will be
ascertained in asthma patients, who have been (existing patient resources) or
will be (to be acquired patient resources) phenotyped with respect to the
response to treatment with the class of asthma medication of interest;5) The
investigators will use a case -control association approach to define specific
genotypes associated with either a salutary treatment response or lack thereof.
(In newly acquired populations they will use transmission disequilibrium
testing); 6) Once genotypes associated with potential pharmacogentic predictive
value are defined they will collaborate with the NIH sponsored Asthma Clinical
Research Network to study patients with specific genotypes to determine if they
provide predictive information about treatment responses; 7) Our approach will
allow us to ascertain the pharmacogenetic basis for the observed variability in
asthma treatment responses.
StatusFinished
Effective start/end date4/1/037/31/05

Funding

  • National Heart, Lung, and Blood Institute

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