Respiratory viral infections,
especially human rhinovirus (HRV) account for approximately 80 percent of
asthma triggers in children. And infants who have HRV infections with wheezing
problems have an increased risk for developing asthma in childhood. But HRV
does not always lead to wheezing illness in children, nor does wheezing illness
cause asthma in all cases. Since asthma is also hereditary, genes probably have
a big role to play.
So, to find out how genes and
wheezing illness caused by HRV or respiratory syncytial virus (RSV) in infancy
are connected in the development of asthma in children, Minal Caliskan and
colleagues at the Department of Human Genetics, University of Chicago, studied
the data from two groups of children -
- 200 children from the Childhood Origins of Asthma (COAST) group
who had at least one parent with asthma and /or respiratory allergies. The kids
were followed from birth to age 6.
- 297 children from the Copenhagen Prospective Study on Asthma
in Childhood (COPSAC) group who had mothers with asthma. These children were followed
from birth to age 7.
In addition the investigation
also included 100 unrelated adults.
The genes in question here are
gene variants in the region of chromosome 17q21 which earlier studies found to
be strongly and reproducibly associated with childhood onset asthma. The
present study investigated the role of expression levels of two 17q21 genes, GSDMB
- the risk for developing asthma was 5-fold in children
with HRV and wheezing;
- the risk for developing asthma was 2-fold in children
with the identified asthma associated 17q21 gene variants;
- the risk for developing asthma was 26-fold in children
with both, HRV with wheezing and asthma genes;
- the overall prevalence of asthma was lower in the
COPSAC cohort than in the COAST cohort, maybe because the rate HRV wheezing
illness was lower in COPSAC group and also because the diagnosis of asthma
required a response to a 3-month course of inhaled glucocorticoids followed by
a relapse after treatment was stopped;
- wheezing caused by respiratory syncytial virus (RSV)
did not show the same interaction;
"The combination of genetic
predisposition and the child's response to this infection has a huge effect,"
said Carole Ober, co-author of the study.
Although scientists are not very
clear on how the genes at the 17q21 locus lead to asthma, they suspect that
ORMDL3 may play a role in viral respiratory infections. To investigate how
exposure to HRV altered expression of the asthma genes 17q21, the researchers
in this study collected blood samples from 100 adults and exposed the
immune-system cells from the blood to HRV. As expected, ORMDL3 showed a huge response by more than doubling
its presence in the exposed cells.
'Over expression of ORMDL3 may
increase the efficiency of the infection or viral replication in respiratory
epithelial cells, which are the site of HRV infection and replication, and
possibly reduce the ability of these cells to repair themselves after HRV
infection,' according to Minal Caliskan, the lead author of this study.
She concluded - 'this study
establishes a role of 17q21 variants in the development of HRV wheezing
illnesses during early childhood and shows that the effects of the 17q21
genotype on the susceptibility to asthma are seen primarily in the subgroup of
children who have had an HRV wheezing illness in early childhood' and suggested
further investigations into the' joint effects of genetic and environmental
risk factors' to understand the mechanisms of complex diseases.
Įaliskan M et al. Rhinovirus wheezing illness and
genetic risk of childhood-onset asthma. N Engl J Med 2013 Mar 27.