Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Understanding Triglycerides’ Role in Coronary Disease

Published: Wednesday, October 09, 2013
Last Updated: Wednesday, October 09, 2013
Bookmark and Share
The study leverages new genetic data from a related genome-wide association study, suggests that lowering triglyceride levels through treatment may help reduce the risk of coronary heart disease.

A team led by Broad Institute researchers has found that triglycerides - the fats that our bodies burn for fuel - play a causal role in coronary artery disease (CAD), the most common form of heart disease and the leading cause of death in the United States. 

Every day, millions of vials of blood are drawn to assess patients’ risk for the disease. These tests measure three biomarkers, or factors in the blood known to be associated with CAD: low-density lipoproteins (LDL cholesterol), high-density lipoproteins (HDL cholesterol), and triglycerides. All three biomarkers are lipids – water-insoluble molecules that are among the structural and functional building blocks of living cells.

“The key question over the years about these biomarkers has been, which ones cause coronary artery disease and which ones are merely reflective of the disease process?” said Broad associate member Sekar Kathiresan, who led the study along with Broad senior associate member Mark Daly, associate member Ben Neale, and first author Ron Do, who is a postdoctoral fellow in Kathiresan’s lab. Kathiresan is also the director of preventive cardiology at Massachusetts General Hospital.

“The reason that question is important is not for prediction, because biomarkers are useful for predicting disease whether they are causal or not,” Kathiresan explained. “The reason we want to distinguish between these factors is for treatment. We really only want to attack the causes of the disease.”

LDL, the so-called "bad cholesterol," has already been proven to cause heart disease and is the target of the well-known, cholesterol-lowering drugs called statins. HDL, the "good cholesterol" once thought to directly reduce risk of CAD, has in recent studies shown no causal connection with coronary artery disease.

The role of triglycerides has remained a matter for debate. While elevated triglyceride levels are seen in patients with CAD, making it an effective biomarker, evidence that these blood fats play a causal role in the disease has been inconclusive, and treatments aimed at lowering triglyceride levels have not yet succeeded in reducing disease risk.

To determine whether triglycerides do, in fact, play a causal role in CAD, Kathiresan’s team looked at 185 variations in the genetic code that have been found to be associated with blood lipid traits. Such variations, called single nucleotide polymorphisims, or “SNPs,” are inherited from one or both parents and can affect the way an individual expresses a given trait.

The researchers looked at these SNPs in over 86,000 people and assessed the degree to which each SNP affected LDL, HDL, and triglyceride levels, as well as CAD risk. They then compared these effects. If SNPs that altered the level of a given biomarker also altered disease risk to the same degree, it could be assumed that the relationship between the biomarker and the disease was causal.

Kathiresan’s team previously applied this approach to LDL and HDL in studies that confirmed LDL’s causal role in heart disease, and cast doubt on any causal association between HDL and CAD. This new study, which relies on new genetic variants identified by the Global Lipids Genetic Consortium (GLGC) in a paper also published this week in Nature Genetics, confirms the previous findings while taking a fresh look at the role of triglycerides.

Kathiresan, who was also one of the leaders of the GLGC study, said that his team observed a pattern of association between triglycerides and CAD that resembled what they observed for LDL: the effects of these SNPs on triglyceride levels were highly associated with their effect on CAD risk, even after accounting for the potentially confounding effect of each SNP on HDL or LDL levels. The data strongly suggest that triglycerides are a causal factor in CAD.

Exactly how triglycerides may contribute to coronary artery disease is still undetermined. LDL cholesterol is known to cause CAD by contributing to the build-up of “plaque” along the artery walls. As these molecules are deposited, they block blood flow through the arteries, which can lead to heart attack. One hypothesis is that the lipoprotein particles that carry triglycerides in the blood stream (so-called triglyceride-rich lipoproteins) may deposit in the heart arteries in a manner similar to LDL.

The researchers suggests that, even as the exact causal mechanisms are worked out, targeting triglycerides for treatment may be an effective strategy for reducing heart disease risk.

“Clinically speaking, one of the ways to prevent a first heart attack or to reduce the risk of a second heart attack in someone who already has heart disease may be to treat patients with medicines that lower the levels of triglyceride-rich lipoproteins,” Katherisan said. “Some drugs that target triglycerides are already being tested; it is now a matter of finding the right mechanism of lowering triglycerides that will effectively reduce disease risk.”

The findings appear this week in Nature Genetics.

Other Broad researchers who contributed to this work include Chi Gao, Gina Peloso, Tõnu Esko, Pierre Fontanillas, Sailaja Vedantam, Joel Hirschhorn, and David Altshuler.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Screen of Human Genome Reveals Set of Genes Essential for Cellular Viability
Using two complementary analytical approaches, scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells.
Monday, October 19, 2015
DARPA Awards $32 Million Contract to MIT, Broad Institute Foundry
A facility at the Broad Institute of MIT and Harvard and MIT that aims to achieve the full potential of engineering biology has received a five-year, $32 million contract from the Defense Advanced Research Projects Agency (DARPA).
Monday, September 28, 2015
Scientists Discover New System For Human Genome Editing
CRISPR-Cpf1 system could disrupt both scientific and commercial landscape.
Monday, September 28, 2015
Broad Institute & Google Genomics Combine Bioinformatics and Computing Expertise
Both companies explore how to break down major technical barriers that increasingly hinder biomedical research.
Thursday, June 25, 2015
CRISP-Disp Leverages CRISPR-Cas9 to Deliver RNA Structures to Targets in the Genome
A team of researchers from the Broad Institute and the Harvard Stem Cell Institute has developed CRISP-Disp, a method that expands on the CRISPR-Cas9 system, allowing researchers to display multiple, large RNA structures on the Cas9 protein.
Wednesday, June 10, 2015
GTEx: Useful Expression For Cancer Research
GTEx Project has recently published several papers reporting on findings from its two-year pilot phase.
Tuesday, May 26, 2015
Single-cell Analysis Hits its Stride
Advances in technology and computational analysis enable scale and affordability, paving the way for translational studies.
Saturday, May 23, 2015
Highly Efficient New Cas9 for In Vivo Genome Editing
New finding is expected to expand therapeutic and experimental applications of CRISPR.
Tuesday, April 07, 2015
Broad Institute of MIT and Harvard and Bayer Healthcare Expand their Partnership
Collaboration to develop therapies for cardiovascular disease.
Thursday, April 02, 2015
In vivo CRISPR-Cas9 Screen Sheds Light On Cancer Metastasis And Tumor Evolution
Genome-scale study points to drivers of tumor evolution and metastasis, provides roadmap for future in vivo Cas9 screens.
Friday, March 06, 2015
Scientists Map the Human Loop-ome, Revealing a New Form of Genetic Regulation
Researchers describe the results of a five-year effort to map, in unprecedented detail, how the 2-meter long human genome folds inside the nucleus of a cell.
Tuesday, December 23, 2014
Disorder in Gene-Control System is a Defining Characteristic of Cancer, Study Finds
Findings indicate that the disarray in the on-off mechanism is one of the defining characteristics of cancer.
Tuesday, December 23, 2014
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Thursday, November 27, 2014
Dramatic Response And Resistance To Cancer Drug Traced
Sequencing reveals why thyroid tumor responded to, and eventually resisted, treatment.
Friday, October 10, 2014
Study Expands the Cancer Genomics Universe
The universe of cancer mutations is much bigger than previously thought, and key cancer genes are still to be discovered.
Tuesday, January 28, 2014
Scientific News
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos