Nav: Home

Rare mutation causes early heart disease and metabolic syndrome

March 01, 2007

New Haven, Conn.--Yale School of Medicine researchers have identified a rare defect in a single gene that poses a substantial risk for metabolic syndrome and early heart disease, the leading cause of death worldwide.

The international study, led by Arya Mani, M.D., assistant professor of cardiology, and Richard Lifton, M.D., chair of genetics at Yale, identifies a new pathway implicated in heart disease. Even though the genetic mutation is very rare, these findings point to new approaches for improving this aspect of health.

"These findings indicate that altered activity of a well-known signaling pathway, Wnt, has large effects on multiple metabolic pathways that contribute to cardiovascular disease," said Mani.

Coronary artery disease (CAD) is commonly caused by metabolic syndrome, which includes a constellation of risk factors such as high low-density lipoprotein (LDL) cholesterol, high triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and diabetes.

This study was based on a large family of Iranian ancestry that had an extraordinary prevalence of early CAD. Among 58 blood relatives, 28 were diagnosed with early CAD at or before age 50 for the men, and 55 for the women. Twenty-three of the 28 died from CAD at young ages. In contrast, relatives without early CAD died at an average age of 81. The relatives with CAD had high LDL, high triglycerides, hypertension, and diabetes, while their unaffected relatives did not. The relatives with CAD also were predisposed to osteoporosis, which is particularly interesting given recent evidence of association of osteoporosis with CAD.

By comparing the inheritance of CAD to the inheritance of each chromosome segment in the pedigree, the team narrowed the location of the disease-causing gene to a short segment of chromosome 12. In this region, they found a single mutation in a gene called LRP6, which acts in the Wnt signaling pathway and which was previously known to be involved in development and in certain forms of cancer. The mutation changed one amino acid in the protein, which the team showed altered the activity of the protein encoded by LRP6.

"The reason for the observed association of multiple risk factors with one another has been a mystery," Lifton said.

"Our findings have implicated the Wnt signaling pathway in the development of many risk factors and early CAD. We expect that studies of the Wnt signaling pathway in patients with early CAD, and metabolic syndrome, will provide new insight into the basic biology of disease causation and allow new approaches to disease prevention."
-end-


Yale University

Related Heart Disease Articles:

Where you live could determine risk of heart attack, stroke or dying of heart disease
People living in parts of Ontario with better access to preventive health care had lower rates of cardiac events compared to residents of regions with less access, found a new study published in CMAJ (Canadian Medical Association Journal).
Older adults with heart disease can become more independent and heart healthy with physical activity
Improving physical function among older adults with heart disease helps heart health and even the oldest have a better quality of life and greater independence.
Dietary factors associated with substantial proportion of deaths from heart disease, stroke, and disease
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
Certain heart fat associated with higher risk of heart disease in postmenopausal women
For the first time, researchers have pinpointed a type of heart fat, linked it to a risk factor for heart disease and shown that menopausal status and estrogen levels are critical modifying factors of its associated risk in women.
Maternal chronic disease linked to higher rates of congenital heart disease in babies
Pregnant women with congenital heart defects or type 2 diabetes have a higher risk of giving birth to babies with severe congenital heart disease and should be monitored closely in the prenatal period, according to a study published in CMAJ.
Novel heart valve replacement offers hope for thousands with rheumatic heart disease
A novel heart valve replacement method is revealed today that offers hope for the thousands of patients with rheumatic heart disease who need the procedure each year.
Younger heart attack survivors may face premature heart disease death
For patients age 50 and younger, the risk of premature death after a heart attack has dropped significantly, but their risk is still almost twice as high when compared to the general population, largely due to heart disease and other smoking-related diseases The risk of heart attack can be greatly reduced by quitting smoking, exercising and following a healthy diet.
Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes
Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy.
Gallstone disease may increase heart disease risk
A history of gallstone disease was linked to a 23 percent increased risk of developing coronary heart disease.
Americans are getting heart-healthier: Coronary heart disease decreasing in the US
Coronary heart disease is one of the leading causes of death in the United States.

Related Heart Disease Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Don't Fear Math
Why do many of us hate, even fear math? Why are we convinced we're bad at it? This hour, TED speakers explore the myths we tell ourselves and how changing our approach can unlock the beauty of math. Guests include budgeting specialist Phylecia Jones, mathematician and educator Dan Finkel, math teacher Eddie Woo, educator Masha Gershman, and radio personality and eternal math nerd Adam Spencer.
Now Playing: Science for the People

#518 With Genetic Knowledge Comes the Need for Counselling
This week we delve into genetic testing - for yourself and your future children. We speak with Jane Tiller, lawyer and genetic counsellor, about genetic tests that are available to the public, and what to do with the results of these tests. And we talk with Noam Shomron, associate professor at the Sackler School of Medicine at Tel Aviv University, about technological advancements his lab has made in the genetic testing of fetuses.