Monday, 26 March 2012


Heart Disease Caused by Genetics? – Valen Angelos (42906689)
Heart disease is the leading cause of deaths in Australia (Reece et al. 2012) which makes studying its causes and looking for treatments very important. A study was conducted recently looking at the causes of a particular type of heart disease, dilated cardiomyopathy (DCM). It found that cases of DCM are linked to a specific genetic mutation. It’s already known that genetic mutations can cause DCM, but these are always rare, usually only occurring in a single family (McNally 2012). There are about 50 different mutations that can cause the disease but even the most common one is only found in 5% of cases (McNally 2012). But this new study found that a mutation in a single gene, TTN, caused DCM in 27% of the cases (Herman et al. 2012).
Dilated cardiomyopathy causes the left ventricle to become enlarged (Figure 1). This weakens the muscle tissue and stops the heart from pumping blood around the body as well as it usually does (Mayo Clinic 2011). This can lead to irregular heartbeats, blood clots and, in severe cases, death (Mayo Clinic 2011). Causes of DCM include lifestyle choices such as alcohol and drug abuse and of course genetic mutation. (Mayo Clinic 2011)
 Illustration showing dilated cardiomyopathy
Figure 1: A normal heart compared with one with dilated cardiomyopathy. Note the enlargement of the left ventricle. (Mayo Clinic 2011)

The gene that this study focuses on is TTN. TTN is used to encode the protein titin (McNally 2012). Figure 2 shows a sarcomere, one of the contractile structures in muscle tissue. (McNally 2012). Titin monitors the sarcomere’s length during contraction and relaxation and relays this information to the rest of the cell (McNally 2012). 27% of patients with cardiomyopathy had titin that was too short as a result of the TTN mutation (Herman et al. 2012). This means that the titin is not be able to signal to the cell when the sarcomere had lengthened or shortened abnormally (McNally 2012). This malfunction causes the heart muscle cells to become damaged from prolonged activity and this would lead to cardiomyopathy.
 http://www.nature.com/nature/journal/v483/n7389/images_article/483281a-f1.2.jpg
Figure 2: A sarcomere, the protein structure that contains titin. (McNally, 2012)

In addition, the researchers found that some of the control subjects also had the TTN mutation. They propose that these individuals may contain other genetic mutations which suppress the TTN mutation, however they are unsure as to how these suppressors work (Herman et al. 2012). This provides room for further research to discover these unknown genes, which may lead to the development of new treatments for patients with cardiomyopathy.
This discovery is noteworthy because it means that patients can be diagnosed with DCM a lot sooner. In the past, you had to sequence all of the different genes that could cause DCM before you knew what the cause was. However, since a large number of the test subjects had this TTN mutation, genetic sequencers can check this gene first. This will hopefully lead to faster, more accurate diagnoses and earlier treatment, leading to better quality of life for the sufferers.

Reference List

Herman, DS, Lam, L, Taylor, MRG, Wang, L, Teekakirikul, P, Christodoulou, D, Conner, L, DePalma, SR, McDonough, B, Sparks, E, Teodorescu, DL, Cirino, AL, Pennell, Pennell, DJ, Graw, S, Merlo, M, Di Lenarda, A, Sinagra, G, Bos, JM, Ackerman, MJ, et al. 2012, 'Truncations of Titin Causing Dilated Cardiomyopathy', New Engalnd Journal of Medicine, vol 366, pp. 619-628.
Mayo Clinic 2011, Dilated cardiomyopathy, viewed 17 March 2012, <http://www.mayoclinic.com/health/dilated-cardiomyopathy/DS01029>.
McNally, EM 2012, 'Broken giant linked to heart failure', Nature, vol 483, pp. 281-282, viewed 15 March 2012, <www.nature.com/nature/journal/v483/n7389/full/483281a.html>.
Reece, JB, Meyers, N, Urry, LA, Cain, ML, Wasserman, SA, Minorsky, PV, Jackson, RB & Cooke, BN 2012, Campbell Biology, 9th edn, Pearson Education, San Francisco.

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