The Genetics Behind Allergic Asthma


Introduction:

As May is National Allergy and Asthma month (and for good reason, as most people tend to experience worsening symptoms during the spring season), it seems only fitting to learn more about these illnesses and their symptoms, and more relevant to this topic, consider how genetics might play a part. As an asthmatic myself, I was once skeptical of the theory that genetics could be held somewhat responsible for my condition--neither my parents nor my grandparents suffered from asthma; in fact, the only member of my family afflicted was my great-grandfather on my mother's side. I believed that it was 100% due to the environment we lived in; the growing statistics of asthma and allergy sufferers served only to prove my point.

Yet, after reading through many research articles and learning about some recent breakthroughs, I could no longer deny the fact that there had to be some genetic links involved. Granted, I still firmly believe that the environment plays a major role and continues to contribute to the rising number of allergic and asthmatic people, but I understand that genetics is also responsible. This, perhaps, is why I decided to concentrate on this topic: to clarify the genetic link of asthma and allergies a little bit better not only for everyone else, but also myself.

As concentrating on both asthma and allergies would probably be a little bit more than I wanted to expound upon, I decided to focus on a subset of asthma: allergic asthma. Allergic, or extrisinic, asthma is the most common form of asthma; it affects over 50% of the 20 million asthmatics and approximately 2.5 million children suffer as well[1] Allergic asthma occurs because the human's immune system tries to overcompromise the effect of allergens, such as dust, cockroaches, cat and dog hairs, trees, etc., entering the bronchioles; bronchospasms occur (in which the muscles around the bronchioles constrict) and the bronchioles are inflammed and coated in mucus.[2] Symptoms can include coughing, wheezing, and tightening chest, and thus, difficulty breathing.



Background/History:

Since it can get quite dreary simply listing facts and such about the background/history, I've prepared a voicethread which is embedded here. The first reference is the one in which I found the dates/actual information and the rest in this section are of the pictures.



[3] [4] [5] [6] [7] [8] [9] [10] [11] [12]




Explanation/Connections:

As summarized earlier, allergic asthma is caused by the tightening of the bronchioles in response to external stimuli (allergens) such as cat dander or dustmites. There is nothing particularly "harmful" about these things in and of itself; it is the asthmatic's response to these allergens that trigger what are known as asthma attacks. The above link can take you to a picture showing the difference between how an asthmatic and non-asthmatic would respond to these allergens.

asthma-britannica.jpg[13]


To get into the details of asthma, asthma is an obstruction to breathing, or air flow, and occurs because of bigger than normal mucus glands which cause thick mucus in the bronchioles due to scarring and inflammation. The bronchioles themselves constrict because the smooth muscle outside of the bronchioles swell due to allergens, such as pollen, dustmites, trees, cut grass, and smoke. In allergic asthma, people intake allergens that eventually go through the inner airways and are consumed by antigen-presenting cells, or APCs, which take parts of the allergen to other cells in the immune system.[14] In normal people, the other cells, known as T(subH)O cells ignore these allergens. But in asthmatic patients, the APCs turn into a completely different type of cells (T(subH)2) and the mechanism for this is not fully known.[15] These cells then produce antibodies, known as IgE, against the allergens, ready in case the need arises to attack when the same allergens appear again. Not surprisingly, the next tie the person intakes these allergens, a massive response is triggered: the cells recognize the same allergen and respond by causing the airways to thicken and fill with mucus and cause bronchospasms, as the person can not breathe due to these occurrences. This hypersensitivity to the allergens is classified as type 1 hypersensitivity.[16]


This animation explains the process visually. The different cells it's talking about (mast cells e.g.) have the same function as the ones above; don't worry about the naming.

Now for how genetics plays a role in asthma: surprisingly, over 100 genes have been associated with asthma in at least one genetic association study; however, there are 25 genes that have been shown to have an effect, as of a study in 2005.[17] Some of these genes include[18]
  • GSTM
  • IL10
  • LTA
  • NOS1
  • TNF
  • CTLA-4
  • LTC4S

Unsurprisingly, many of these genes are related to the immune system and to controlling inflammation. However, later studies have shown that not all of these genes (considering the 25) have been linked in all populations of people tested, which leads many to believe asthma could be a collection of many different illnesses and genes only have a role in a certain subset of asthma.[19]


While there are several connections that can be made between this and the genetics that we have learned in class, I will just describe two of them:

1) Pedigrees: We learned in genetics that a pedigree is a pictorial representation of of a family history that outlines the inheritance of one or more traits or diseases. The patterns in a pedigree can help to reveal the mode of inheritance and whether the gene is dominant or recessive. A famous pedigree is Queen Victoria and the British Royal Family's pedigree on hemophilia that we studied in class. Surprisingly, there are pedigrees of asthma and allergies. One of them is the famed DeCode asthma pedigree figure which looks completely different from the pedigrees we have studied. I have included that one as well as another more traditional-looking one; this one shows a tendency for asthma, allergies, and eczema.
DeCode pedigree[20]
[[@http://www.hsl.virginia.edu/historical/eugenics/assets/chart_pedigree_allergy2.jpg|Traditional Pedigree[21] ]]


2) Mutations: We have extensively learned about mutations and that they are changes in the DNA because of replication errors and that they can be inherited and passed on and that they can cause phenotypical as well as genotypical differences in the individual. One recent study[22] show that a genetic mutation in a particular gene indicted for causing severity in asthma, may in fact be the trigger to causing the asthma. This gene is called the CHI3L1gene, which produces YKL-40 protein. The study found that a mutation in this gene is associated with high YKL-40 protein levels in the blood (which studies have shown that people with severe asthma have elevated levels of this protein YKL-40). While not everyone with high YKL-40 protein levels have asthma, an offspring with the mutated CHI3L1 gene from both parents was twice as likely to have asthma, according to the lead researcher, Carole Ober. I have tried to find the exact type of mutation that occurs, but have been unable to do so.




Social/Ethical Implications:


vsh0483l.jpgmban2616l.jpg[23] --For both cartoons
Allergic asthma affects millions of people across the globes. Here are statistics[24] to prove it:
  • Asthma strikes 1/15 Americans and nearly half of those have allergic asthma.
  • Asthma is the most common chronic condition among children. Interestingly enough, while it is more common in male than female children; more female adults have asthma than male adults.
  • If only one parent has asthma, chances are 1 in 3 that each child will have asthma. If both parents have asthma, it is much more likely (7 in 10) that their children will have asthma.
  • The total "costs" of asthma is nearly 18 billion--10 billion for "direct" costs including hospitalizations, paying for medications, etc. and 8 billion for lost and unpaid for work days and death.
  • While one would assume that better medication would lead to better control over asthma, this is an incorrect assumption: since 1980, asthma death rates have increased more than 50% overall and the death rate for children has increased by nearly 80% since 1980.
  • Asthma is the Number 1 cause of school absenteeism in children; children miss nearly 14 million days of school combined together.
  • And to top it all of...every single day in the USA:
    • 40,000 miss school or work due to asthma.
    • 30,000 suffer an asthma attack.
    • 5,000 visit the ER for asthma-related reasons.
    • 1,000 are admitted to the hospital due to asthma.
    • 11 die from asthma.

Therefore, obviously any genetic discoveries which can better reveal how asthma is passed down from parent to child will have social implications in that many people will be involved and will try to prevent asthma from affecting their children. And, as clearly shown, regardless of what role genetics does play in allergic asthma, asthma already has HUGE social implications in society today.


While researching, I did not exactly find any "ethical controversies" that completely pertained to asthma but I found a few articles that did involve some bioethical issues. One[25] of those articles had to do with measuring the ability of asthma-stricken teenagers to choose to participate in a scientific study. They rated whether they went more with the decision of their parents rather than their physicians; surprisingly, the study showed that these teenagers took the word of the physicians more often than not. While interesting, this study did not have much to do with genetics or asthma. The reason this was construed as controversial was that because, rather than let the guardian or parent have full authority of whether or not the child should participate, the child himself/herself would get to choose with only minimal guidance from elders. This could be frowned upon because many believe that a child's decision-making part of the brain is not fully developed until the 20s and that the child does not have the world experience and knowledge to make the "better" decision. The other study[26] had to do with the bioethics of using placebos versus the actual medicine in real-life situations; the one mentioned in the study used a saline solution (placebo) to determine whether the asthmatic/allergic man's symptoms were his body's response to immunotherapy or psychosomatic. After receiving said solution and reporting symptoms of chest tightening, this was discontinued. The ethical quandary in this was whether or not to tell the patient--or any patient for that matter--that he or she had been receiving the placebo and whether or not he or she should have received the placebo in the first place. This is a problem still under scrutiny in science and is not endemic just to this field.



Potential Futures:


There are several possibilities that genetics could play in the future concerning allergic asthma. As we now know, there are different genetic subtypes of asthma. Genetic testing, in the future, could possibly reveal what subtype a person has, and then that person could receive specific medical treatment based on that result. Currently, there are several different types of rescue inhalers but not all of them are effective for the same person (I would know; I have tried several of them. Combivent does not work well with me for some reason while Proventil does). Therefore, genetic testing could determine which rescue inhaler a person would be most receptive to; other genetic tests could determine the likelihood of side effects based on medications for asthma preventions.

While this is not necessarily new, people have been finding ways to try to get rid of allergies, namely food allergies. As this video shows, it is possible to overcome food allergies like peanut allergy, by slowly developing immunity the same way that a vaccine helps one to develop immunity against the disease--by giving the patient just a little bit of it.

[27]

One particular resource[28] has an extremely interesting vision of the role of genetics in the future. While admitting that only about a third of the possible link between genetics and allergic asthma has been discovered as of right now, this optimistic perspective believes that the research programs will have discovered the other two-thirds of information within five years or so. While I find this to be a little overly optimistic, I do beliee that, with all the funding going into genetic research (while it may not be in the US, it is becoming more important in other countries) and the awareness of asthma and allergies, it is probable that remaining breakthroughs can be made in the upcoming century. The article goes on to state that all genes or loci of genes which might result in asthma need to be extracted, sampled, and then examined thoroughly. Results can show that these different genes will interact differently depending on the environmental variables, which will not only prove how both genes and the environment can cause asthma, but will also have important implications for treatment. The article also brings up an interesting point in that people who are genetically predisposed to asthma are perhaps more susceptible to helminth (parasitic worms/flukes/tapeworms) infections. While this seemingly random connection may not seem important, the truth is that people with helminth infections more likely than not live in third-world countries or underdeveloped countries due to the unsanitary conditions, the manual labor and proximity with dirty water and infested soil that the citizens may have, and bad hygiene due to no knowledge of hygiene or no money to afford well-keeping. Because this is a genetic adaptation over time, it stands to reason that even people who have lived in urbanized countries may be more susceptible to asthma. Clearly then, there need to be more studies that can determine better the development of asthma in individuals transferring from rural to urban societies.
  1. ^ http://www.aafa.org/display.cfm?id=8&sub=16
  2. ^ http://www.webmd.com/asthma/guide/allergic-asthma
  3. ^ http://www.allergyasthmaspecialist.com/education/history_of_allergy.html
  4. ^ http://arthritisfoundationwpa.files.wordpress.com/2010/03/allergy.jpg
  5. ^ http://www.solarnavigator.net/geography/geography_images/Egypt_Maler_der_Grabkammer_des_Ramose_tomb_painting.jpg
  6. ^ http://www.easypedia.gr/el/articles/m/a/i/Εικόνα~Maimonides-2.jpg_500f.html
  7. ^ http://www.rinklanddaylilies.com/files/Rose_Fever_7_16_06.jpg
  8. ^ http://www.kidsaware.co.uk/imagesproducts/fridgemagnet-egg.jpg
  9. ^ http://www.umass.edu/tei/TEI/images/UMassEnv/pollen.gif
  10. ^ http://www.allerresponz.com/ige.GIF
  11. ^ http://www.asthme-quebec.ca/eng/asthma/img/glossaire2.jpg
  12. ^ http://unemployednyc.files.wordpress.com/2009/07/claritin.jpg
  13. ^ http://wockhardthospitals.files.wordpress.com/2009/08/asthma-britannica.jpg
  14. ^ http://en.wikipedia.org/wiki/Pathophysiology_of_asthma
  15. ^ http://en.wikipedia.org/wiki/Pathophysiology_of_asthma
  16. ^ http://en.wikipedia.org/wiki/Pathophysiology_of_asthma
  17. ^ http://en.wikipedia.org/wiki/Asthma#Genetic
  18. ^ http://en.wikipedia.org/wiki/Asthma#Genetic
  19. ^ http://en.wikipedia.org/wiki/Asthma#Genetic
  20. ^ http://www.learner.org/courses/biology/images/archive/fullsize/1514_fs.jpg
  21. ^ http://www.hsl.virginia.edu/historical/eugenics/assets/chart_pedigree_allergy2.jpg
  22. ^ http://healthlibrary.epnet.com/GetContent.aspx?token=a4c1f00b-d245-44f2-a90e-20b047f84a6a&chunkiid=285363
  23. ^ http://www.cartoonstock.com/directory/a/asthma.asp
  24. ^ http://www.aafa.org/display.cfm?id=8&sub=42
  25. ^ http://pediatrics.aappublications.org/cgi/content/abstract/118/2/e356
  26. ^ http://www.jaapa.com/the-ethics-of-using-placebos-for-diagnosis-and-treatment-in-clinical-practice/article/159033/
  27. ^ http://www.youtube.com/watch?v=CoWNbulp45c&feature=PlayList&p=7DEB54F2007F5F35&playnext_from=PL&playnext=1&index=20
  28. ^ www.who.int/genomics/about/Asthma.pdf