Gene Expression and Genome Wide Association Study on remission of asthma

Recently, we have shown that some asthmatics show complete asthma remission in
adulthood. Investigating the mechanisms leading to this spontaneous remission
of asthma may provide new avenues for better understanding of asthma remission
and may eventually lead to new intervention strategies. In 2008 we have started
a genome wide association study (GWAS) on asthma. Additionally one can search
for expression of genes in tissue, like epithelial cells. Some of the asthma
patients (59) participating in the GWAS were in clinical or complete remission.
In 1987, a group of asthmatics visited the UMCG for a follow-up study of R.J.
Roorda, the Roorda cohort. The patients all had childhood asthma with
hyperresponsiveness as a child. We now are interested in investigating who is
in remission of asthma and to search for genetic background of this remission
by gene expression profiling in epithelial cells. The NORM study will be used
as a control population and all participants have been fully screened.

Main objective: To investigate differential gene-expression in nasal epithelium
of asthmatics in complete remission, in clinical remission, not in remission
and healthy controls.

We study two cohorts with new clinical and functional characterization:
1) The Roorda cohort: A follow-up study of the Roorda cohort (age > 18 years).
Patients are asked to visit the UMCG to perform spirometry with reversibility,
metacholine challenge test, NO measurements, skin prick test, blood parameters
of a.o. allergy and DNA isolation and a nose brush. In subjects who still have
currently active asthma, peripheral blood mononuclear cells will be isolated
and stored for T lymphocyte purification. IL1RL1 receptor expression on T cells
will be assessed using flowcytometry. Moreover, using its ligand IL33, we will
stimulate the IL1RL1 receptor and investigate the strength of IL1RL1 receptor
signal transduction using activation of intracellular signaling intermediates
including ERK, p38 MAP kinase and NF*B as an outcome. We will relate both
outcomes to IL1RL1 genotypes.
2) DAG cohort: Patients in clinical or total remission in the DAG cohort will
be asked to perform NO measurements, a nose brush and determination of a.o.
allergy in blood.

The burden to the individual participants will be performing a reversibility
test, metacholine challenge test, NO measurements and blood samples and nose
brushes that will be taken. This implies that the person may experience some
breathlessness that will fade away immediately after giving a bronchodilator
after the metacholine challenge, and they will experience some discomfort when
blood samples and nose brushes are taken. It is expected that the burden of
these measurements lasts for a short period of time (i.e. 15 minutes).