Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Childhood Asthma Tied to Combination of Genes and Wheezing Illness

Published: Thursday, March 28, 2013
Last Updated: Thursday, March 28, 2013
Bookmark and Share
Interaction between gene and environment predicts disease onset.

About 90 percent of children with two copies of a common genetic variation and who wheezed when they caught a cold early in life later developed asthma by age 6, according to a study published in the New England Journal of Medicine.

These children, all from families with a history of asthma or allergies, were nearly four times as likely to develop the disease as those who lacked the genetic variation and did not wheeze. The effects of each—the genetic variation and wheezing illness caused by a human rhinovirus infection—are not merely additive but also interactive, the authors say.

The genetic marker studied, a variation on chromosome 17, is common. Half of the children in the study had one copy, and 25 percent had two. Colds caused by human rhinoviruses also are extremely common, affecting almost all infants. But the combination of genetic risk plus the wheezing response to rhinovirus infection by children under age 3 was tightly linked to the development of asthma by age 6.

“We found that the interaction between this specific wheezing illness and a gene or genes on a region of chromosome 17 determines childhood asthma risk,” said study author Carole Ober, the Blum-Riese Professor of Human Genetics. “The combination of genetic predisposition and the child’s response to this infection has a huge effect.”

Wheezing caused by respiratory syncytial virus (RSV), a more serious but less common childhood infection, did not show this same interaction.

Several genome-wide association studies have linked asthma to genetic variation on a region of chromosome 17, referred to as 17q21. Although this variation applies primarily to early-onset asthma, it still “dwarfs every other asthma-related genetic risk factor,” Ober said.

Exactly how the genes and viral infection interact to cause asthma is unclear. Two genes in the 17q21 region may play a role. One of them, known as ORMDL3, is the “most likely candidate,” Ober said. The protein produced by ORMDL3 is found in the endoplasmic reticulum membrane, the same component of airway cells that rhinovirus uses to makes more copies of itself. Less is known about the function of the second gene, GSDMB.

The researchers studied two carefully monitored cohorts of children from families at high risk for asthma. All of the 200 children in the COAST cohort, based at the University of Wisconsin under the leadership of Robert Lemanske, principal investigator of the project, had at least one parent with asthma, respiratory allergies or both. They were followed from birth and evaluated for asthma at age 6. The 297 Danish children in the COPSAC cohort were born to mothers with asthma and evaluated for asthma at age 7.

The researchers first investigated the links between genes, wheezing with viral infection and asthma in the COAST group, in which they found significant interactions. Less than 30 percent of children in this group who lacked the asthma-related genetic marker were subsequently diagnosed with the disease, compared to 40 percent of children with one at-risk allele and 50 percent with two. Children who had two copies of the asthma-related genetic variation also had far more HRV-related wheezing illnesses.

When the researchers combined both factors, the difference was striking. Only about 25 percent of children who had no wheezing illness from HRV developed asthma. About 40 percent of those who wheezed in the first three years of life but lacked the risk-related genes got asthma. That increased to nearly 60 percent for those with one copy of the asthma-related allele and to 90 percent for those with two copies.

Next they sought to replicate that finding in a similar group, but from a different continent. Although the overall asthma prevalence, based on slightly different criteria in the Danish cohort, was lower, the more-than-additive association between the at-risk genotype, wheezing illness in early life and asthma diagnosis persisted.

To see how exposure to HRV altered expression of genes associated with the 17q21 marker, the University of Chicago researchers recruited 100 normal adult volunteers, collected blood from them and exposed immune-system cells from the blood to HRV. The leading suspect, ORMDL3, had the most robust response, more than doubling its presence in exposed cells.

This result suggests that “higher expression of ORMDL3 may increase the efficiency of the infection or viral replication in respiratory epithelial cells,” according to the study’s first author, Minal Çalışkan, a graduate student in Ober’s laboratory.

“This is the site where rhinovirus infection and replication occur,” she explained. “Up-regulation of this gene may lessen these cells’ ability to repair the airway after an HRV infection, a feature associated with asthma. Our next project is to look more closely at this process in airway epithelial cells.”

What can parents do to prevent early onset asthma? At this point, “nothing that we know of,” Ober said. Parents can’t prevent their children from catching colds, but “perhaps they could work with their pediatricians to find proactive ways to prevent wheezing in young children with the asthma genotype.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Friday, July 31, 2015
University of Chicago to Establish Genomic Data Commons
First-of-its-kind facility expands access to large-scale cancer genomic data.
Wednesday, December 03, 2014
Two Mutations Triggered an Evolutionary Leap 500 Million Years Ago
Researchers discover just two mutations set the stage for the evolution of modern hormone signaling.
Wednesday, June 26, 2013
New Technique Reveals Unseen Information in DNA Code
Scientists have developed and tested a technique to distinguish between two modified forms of cytosine.
Friday, May 18, 2012
Scientific News
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
Understanding the Molecular Origin of Epigenetic Markers
Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!