Asthma is a disorder of the airways in the lungs. When someone has an airway attack:
An ongoing biological debate revolves around the issue of nature versus nurture. This debate basically revolves around the question of whether your genes or your environment have a greater impact on a person's life. Many studies have been conducted and the question is still not answered. Until recently, asthma was always considered to be environmentally linked. In other words, a person has asthma based on air quality and environmental triggers and not because of hereditary links. However, this view is changing as evidence is arising that asthma may be gene linked.
For tips to avoid such triggers, http://www.wellpathways.com/about_asthma/triggers.asp
In Arizona, a study was conducted where researchers examined 344 families to see if asthma runs in families.
|Families with neither parent having asthma||6% of the children had asthma|
|Families with one parent having asthma||20% of the children had asthma|
|Families with both parents having asthma||60% of the children had asthma|
This reveals a strong correlation between asthma and genetics.
When studying the relationship between genetics and anything, twins are excellent candidates for research. Identical twins have the same genetic makeup while fraternal twins (non identical) do not. In 1995 Sarafino and Goldfedder conducted research to prove that both genetics AND the environment play a role in the appearance of asthma.
In this study 325 pairs of twins were examined. Among these twins, 84 pairs were found where at least one of the twins had asthma (these were the subject of this study). Of the 84 pairs, 39 were identical and 55 were fraternal. The data collected is as follows:
Type of Twin Pair
Number of Twin Pairs
Twin pairs where both twins had asthma
|Identical Twins||39||59% (23 of 39 pairs)|
|Non-Identical Twins||55||24% (13 of 55 pairs)|
This experiment proves the interrelationships between the environment and asthma. If asthma was solely a genetic condition, identical twins (who have the same genes) would have the same chances of developing asthma. But this study shows that in 41% of cases only one identical twin will develop the condition. Similarly, if asthma was solely governed by environmental factors, identical twins would have the same chances of developing asthma as non-identical twins but this study shows that the chances of developing asthma are more than twice as high if twins are identical. These research findings imply that rather than inheriting asthma itself, we inherit a tendency to develop asthma. And this inherited tendency will only come to fruition if we are also exposed to the environmental stimuli that trigger asthma.
As more research is being conducted, more researchers are agreeing with the above statements and arising to the conclusion that your genetic code may predispose you to being susceptible to asthma. Therefore, asthma results from nature AND nurture.
The island of Tristan DA Cunha, located located in the South Atlantic Ocean between Africa and South America, has been the focus of the genetic roots of asthma. The population and asthma, can be mapped out to the original settlers (eight men and nine women) and after a volcanic irruption in 1961, the entire community went under investigation. The reason this island is a candidate to test for the relationship between genetics and asthma is because of the high proportion of inbreeding and high prevalence of asthma. "The level of inbreeding is so high that all the islanders are cousins and on average two siblings are cousins according to 50 different pathways." (Zamel, 1995) The study was conducted in 1993 when the population was 301. A history of respiratory and allergy symptoms were obtained by questionnaire, allergy skin testing and blood testing were conducted.
272 subjects participated in the study and the results obtained were:
|No evidence of Asthma||Partial or questionable evidence of Asthma||Strong evidence of Asthma|
|Number of subjects||120||96||56|
|Percent of Population||44%||35%||21%|
Note: the group that had no evidence of asthma was composed mainly of the younger citizens who may develop asthma in the future. For a more precise evaluation of the prevalence of asthma in this community, the younger subjects would have to be followed for several years to see if they develop asthma. Only once this is done can a true evaluation of the nature of asthma on this remote island be evaluated properly.
In addition, half of the population tested positive to being sensitive to house dust mites and 40% were sensitive to cat fur. However, there have been no cats on the island for 20 years. Many of those found sensitive have never been exposed to a cat in their life!!! Thus showing a genetic tie to asthma and allergies.
For more information on this study, go to http://www.zamel.ca/tristan_article.htm
One thing is certain about genetics and asthma. There is no one "asthma gene". Several genes interact and cause susceptibility to asthma. Keep in mind, that one may have the genes to predispose him/her to asthma without ever suffering from its symptoms. The genes may never be expressed because of lack of environmental stimuli. Because of the many interactions between genetic predisposition, environment and gene interactions, genetic research is very complicated. However, progress is being made and researchers claim to have found certain genes that are one of the causes in asthma in many cases.
A study led by researchers Respiratory Cell and Molecular Biology (RCMB) at the University of Southampton has found success in finding a connection between a specific gene and asthma. This gene is referred to as ADAM33 located on chromosome 20 and is expressed in lung and muscle cells. The ADAM33 gene is believed to be related to asthma as it causes the airways to over-respond and constrict airway passage.
Several other genes on specific chromosomes have been discovered to affect one's susceptibility to asthma. The research involved in such experiments are incredibly complex. One such experiment, Microarray profile of differentially expressed genes in a monkey model of allergic asthma by Zou, Young, et. al. This experiment involved monkeys with previous allergies and inducing asthmatic attacks. After being challenged (by inhalation of A. suum antigen or given interleukin-4 (IL-4) treatment - techniques believed to induce asthma), their lung tissue was collected after 4, 18 and 24 hours, and analyzed. Each of these samples was compared to normal, unchallenged monkey lungs, or the control group.
This experiment utilized a new technique was used for analysis, viewing cDNA on microarrays. cDNA is special in that it contains only introns (protein coding information) and is therefore very valuable in experiments and leads to the identification of the gene in question. Unlike RNA that is complementary to DNA and contains both exons and introns (coding and non-coding information - because of the extra information, it is much more difficult if not impossible to identify the genes).
"Microarray technology offers a new opportunity to gain insight into global gene-expression profiles in asthma, leading to the identification of asthma-associated genes. Microarrays are a 'gene-chip'-based technology in which cDNA sequences representing individual genes are spotted on glass slides at high density. These sequences are then hybridized to cDNA probes derived from paired RNA samples of interest. The two sets of cDNA probes can be labeled with two different fluorescent dyes. The competitive hybridization of a fluorescently labeled probe pair to a microarray enables a comparison of the relative abundance of transcripts of that gene in each sample. In this way, microarrays can detect the differential expression levels of thousands of genes simultaneously."
When someone has an asthma attack, it is believed that different genes are being expressed that are related to airway constriction. For example, one may have the genes that predispose him/her to asthma but without ever being exposed to a trigger for asthma, those genes may never be expressed and the person may never have an asthma attack. After inducing an asthma attack on these allergic monkeys (who are likely to have the genes related to asthma is asthma is indeed gene linked), the scientist cause any genes that may be related to asthma to be expressed. Upon expression of these genes, they will appear different than those of control monkeys on the microarray profile.
The data from this experiment is very complicated (if interested look at full article) but in summary, these microarrays were examined as clusters and at least five groups of genes were found with unique expression patterns. In other words, there is a great possibility that these genes they found are linked to asthma.
For the full article, go: http://genomebiology.com/2002/3/5/research/0020/
This research is very important
to the prevention of asthma as people can be helped with new medications that
directly target the causative genes. Again I want to stress that one's genetic
makeup does not cause asthma but makes one more susceptible to it. An environmental
stimuli is necessary for the activation of asthma. Asthma is more likely to
arise in people with the genetic disposition but may also arise due to excessive
environmental stimuli. Nature and nurture is at work.
Microarray profile of differentially expressed genes in a monkey model of allergic asthma
Jun Zou1 , Simon Young1, Feng Zhu1, Ferdous Gheyas2, Susan Skeans1, Yuntao Wan1, Luquan Wang3, Wei Ding3, Motasim Billah1, Terri McClanahan4, Robert L Coffman4, Robert Egan1, Shelby Umland1
1Department of Allergy, Schering-Plough Research Institute, 2015 Galloping
Hill Rd, Kenilworth, NJ 07033, USA
2Department of Biostatistics, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
3Department of Bioinformatics, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
4DNAX Research Institute, 901 California Ave, Palo Alto, CA 94304, USA
Correspondence: Jun zou. E-mail: firstname.lastname@example.org
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.
Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP.
Genome Therapeutics Corporation, 100 Beaver St, Waltham, Massachusetts 02453, USA.
Nature 2002 Jul 25;418(6896):426-30