A new study involving researchers at the Scripps Translational Science Institute (STSI) and Scripps Health patients reveals major scientific progress in understanding the mechanism of heart disease at the molecular and genomic levels. STSI is an initiative of Scripps Health in collaboration with The Scripps Research Institute.
The study findings establish a link between coronary artery disease (CAD) and genetic susceptibility resulting in an abnormal inflammatory signaling response in a segment of the genome on chromosome 9 (9p21). The discovery sheds new light on the causes of heart disease and opens the door to developing improved approaches to control inflammation. The results from the study will be published Feb. 10 in Nature and also on the journal's website at www.nature.com/nature.
"The hope is that in the future we can find better ways to control inflammation for patients carrying these sequence variants, which may ultimately reduce their risks of heart attacks," said Dr. Eric J. Topol, a corresponding co-senior author of the paper and Chief Academic Officer at Scripps Health. "This was an extraordinary hunt to find how the risk DNA variant was exerting its effect, and it turned out to be quite remote through a gene known as STAT-1, a vital mediator of inflammation."
The findings are significant, as heart disease is the No. 1 killer of adults in the United States. Each year more than 1 million people in the United States have heart attacks, a complication of coronary artery disease, according to the Centers for Disease Control and Prevention.
Prior genome-wide association studies have identified eight genetic variants in a region of chromosome 9 known as 9p21. These genetic variants – known as single nucleotide polymorphisms (SNPs) – in the 9p21 gene desert are strongly associated with CAD and other vascular diseases.
"We had been perplexed as to how the specific location of genome has influenced not just heart attacks but abdominal aortic aneurysms and intracerebral artery aneurysms --so not just atherosclerosis by any means," said Dr. Topol. "Now we know it has to do with inflammation of the artery wall."
For the study, investigators analyzed the genetic profiles of 50 adults of European ancestry that were taken from a pool of 244 self-reported Caucasian males who were enrolled in the STSI (www.stsiweb.org) biobank repository. Of this group, 25 samples had genetic risk markers for CAD, 24 samples had non-risk CAD genetic markers and one individual was non-risk with a mixed genetic marker.
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