 |
YOUR GENES AND YOUR ASTHMA
We have known for a long time that asthma and allergies run in families. The increase in incidence of a disease within families can indicate that genetic factors play a role in predisposing to the disease.
The results of many studies have established that allergy, and allergic disease such as asthma, rhinitis and eczema, have strong genetic components.
Family studies have also suggested that "end organ sensitivity" or which allergic disease an allergic individual will develop is controlled by specific genetic factors, different from those that determine susceptibility to allergy per se. For example studies show that the risk of asthma in children is increased if the parents themselves are asthmatic rather than just allergic, i.e. in addition to a genetic predisposition to allergy, which alters susceptibility to asthma, there are also genetic effects that relate soly to asthma and possibly regulate susceptibility of the conducting airways to both allergic and environmental induced inflammation.
So studies of families can tell us that genes are important in asthma, but when it comes to developing asthma they also tell us that there are lots of different genes that are important in determining whether you will get asthma as well as important environmental factors. It is the interaction between the genes and the environment as people grow that determines whether asthma develops or not.
What can genetic case studies of asthma tell us?
The main goal of research into genetic factors underlying the development of asthma is to provide a greater understanding of the fundamental mechanisms underlying the disease. there are several ways in which genetics can help us understand this:
(i) Insights into underlying disease biology: Identification of small genetic changes that are associated with increased susceptibility to asthma tells us that the importance of that gene in question (and the biological pathways in which it lies) are important in causing asthma. This may then lead to development of specific new drugs both to relieve and prevent symptoms.
(ii) Targeting of therapy: Identification of genetic risk factors may allow the sub-classification of asthmatics into groups who while all have asthma, actually have different underlying disease pathology. This may aid in the selection of appropriate drug treatments for patients. Genetic variation in the targets of asthma therapies or the enzymes that breakdown drugs, may influence how well you respond to your asthma medication or risk of suffering side effects. This may help doctors choose the right medication to treat your asthma.
(iii) Predicting risk: The identification of genetic markers of asthma susceptibility may allow early indentification of susceptible children, allowing them to be targeted at early age for both preventative therapy and environmental intervention such as avoidance of allergen exposure, Genetic screening in early life may thus become a practical and cost effective option in preventing asthma in the future.
What do we know about the genes that predispose to asthma?
One of the first molecular studies carried out to try and identify genes for asthma was undertaken in 1989 at Oxford Univesity by Professor Cookson and his colleagues. Since then there have been many studies that have looked for genes that predispose to asthma either by examinaing the whole genome (genome scan) or by look at specific genes chosen becausewe know the gene product is involved in the disease process. These studies have begub to identify genes that predispose to allery and asthma.
There have been at many genome scans undertaken to identify genes for allergic diseases and a large number of loci (regions of the genome) identified as being linked (inherited with the disease in families) to a range of atopy and asthma phenotypes. Despite this, it has proved difficult to identify the genes that underlie peaks of linkage, as this process requires large well phenotyped cohorts for statistical power, sequence information of the genomic region in question, and maps of genetic markers.
However with the publication of the sequence of the human genome, the rapid increase in markers depositied in databases and improvements in technology the identification of the gene ADAM33 by the Southampton research group in collaboration with colleagues from Genome Therapeutics and Schering-Plough in the United States using familes recruited from around Southampton.
Will it be possible in the future to make accurate prediction of risk for asthma based on an individual's genetic make-up?
In some respects in clinical practice this is done by taking into account family history, however it is hard to be certain whether testing of a series of genetic variants to accurately predict risk and target preventative therapy will be possible for asthma. This uncertainty reflects the complex interactions between different genetic and environmental factors required both to initiate asthma but also modify severity of asthma that a patient has. What is certain is that we are not at this stage yet for asthma but the use of genetic information in clinical decision making or "genomic medicine" is becoming more and more prevalent and we do not know what the future holds.
The Southampton University Asthma Genetics Group
The Southampton University Asthma Gentics group is an inter-divisional research group being part of the Respiratory Cell and Molecular Biology Sub-Division and the Human Genetics Divisions of the School of Medicine.
Studies of the genetic basis of asthma have been undertaken in Southampton since 1989. Professor Stephen Holgate and Professor Newton Morton have undertaken linkage studies in a total of 240 families from the Southampton region funded by MRC. More recently we have undertaken a colloborative project with Genome Therapeutics Corporation (Waltham, MA, USA) and Schering-Plough to identify novel asthma susceptibility gebes which led to identifying ADAM33 as an asthma gene.
The group is lead by Dr John Holloway and some of the current research carried out by membes of the group and other people in the University includes:
Studies of ADAM33 in asthma (Dr John Holloway and Julie Cakebread)
Impact of genetic varitation on leukotriene production and rezones to anti-leukotrience drugs such as Singulair (Dr. Sampson, Dr Holloway, Lanping Hao and Dr Sayers)
Genetic and molecular regulation of Interleukin 13 receptors (Dr Konstantinidis and Dr Andrews)
genes and response to air pollution (Dr Ian Yang, Dr Holloway and Professor Holgate)
Back
|
|
|
|
|
|
|
