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Topol on Genomics

Exciting Advances in Cardiovascular Genomics

Eric Topol, MD, Genomic Medicine, 08:53PM Sep 11, 2011

Eric Topol, MD: Director, Scripps Translational Science Inst.


Two papers published on September 11, 2011, in Nature Advance Online -- one on sporadic thoracic aortic aneurysm and dissection (STAAD) and one on hypertension -- have significant implications on the future of therapy and prevention, especially for thoracic aneurysm.


Le Maire SA, et al. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet. 11 Sept 2011 [Epub ahead of print]

The International Consortium for Blood Pressure Genome-Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 11 Sept 2011 [Epub ahead of print]



Below is a transcript of Dr. Topol's post "Exciting Advances in Cardiovascular Genomics." We look forward to your feedback.

I'm Eric Topol and I want to discuss two very exciting publications in the September 11th issue of Nature Genetics that are on cardiovascular breakthroughs in genomics. One of them is on sporadic thoracic aortic aneurysms and dissections, the acronym STAAD, and the other is on hypertension.

The paper on thoracic aortic aneurysms and dissection is a real breakthrough. We have known for many years that Marfan syndrome is related to a gene fibrillin-1. Now, for the first time, several hundred cases and controls of varied types of aortic dissections and aneurysms  type 1 or type 2, with or without bicuspid aortic valve  were compared with suitable controls by genome wide association. The only gene that proved to be important was fibrillin-1.

That tells us that common variants in the same gene as Marfan's is related to the sporadic types of aortic dissection, all the different types of aortic dissection and aneurysm. That's really exciting because we know there's a therapy that's been validated with further work being done currently, losartan, which blocks TGF, transforming growth factor 1 signaling, and also there is investigation with metalloproteinases and inhibiting the ERK-1 gene pathway. So, it looks like we could potentially screen for people who have either risk or actual aortic aneurysm dissection to see whether or not we might be able to change the natural history with drug therapy. This needs more work and proof, but it's really very exciting.

The other major paper in cardiovascular genomics is on hypertension. Here, 200,000 people were looked at by a meta genome wide analysis study by Aravinda Chakravarti and many colleagues around the world; Chakravarti is at Johns Hopkins. What is exciting here is that now 29 different genomic loci  16 new ones and 13 old ones (recent ones, but considered old)  have been shown to now associate with hypertension.

Why is this important? Many of these are novel pathways  atrial natriuretic peptide has been established, but many are new. This is potentially very exciting because the rare variants in these loci may be particularly high penetrant related to hypertension and a new opportunity of developing drugs in hypertension may come out of this.

With over a billion people in the world with hypertension, it's really great to see the progress being made in the loci associated with common and very important traits. These loci that were discovered and reported in this recent paper were also associated with cardiovascular outcomes, including left ventricular mass and thickness, and other related outcomes to show that this is not just hypertension, but also the sequelae of hypertension.

There is exciting progress in cardiovascular genomics with implications for therapy in the future, particularly more imminent, those with aortic dissection and aneurysm. Things are looking up in the cardiovascular world. I look forward to your comments. Thanks very much for your attention.


Poll: Would you consider screening patients who have sporadic aortic dissection or aneurysm (not Marfan's) to see if they have fibrillin-1 gene variants? No|Yes, so I might use losartan|Yes, to sort out the diagnosis|Yes, for multiple reasons|Unsure|
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About This Blog

Disclosure: Eric J. Topol, MD, has disclosed he is on the scientific advisory board of Gilead Sciences and an advisor to Quest Diagnostics.

  • Eric Topol

    Director of the Scripps Translational Science Institute and Chief Academic Officer for Scripps Health. Professor of Genomics at The Scripps Research Institute and fully active clinically as a cardiologist at Scripps Clinic. Elected to the Institute of Medicine of the National Academy of Sciences, and voted the #1 Most Influential Physician Executive in the United States for 2012 in a poll conducted by Modern Healthcare. Author, Creative Destruction of Medicine.

The content of this blog does not necessarily reflect the viewpoints of Medscape.
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