Mutation leads to combined hyperlipidemia; genetic targeting may reverse it

February 5, 2014 by Helen Dodson
Mutation leads to combined hyperlipidemia; genetic targeting may reverse it
Credit: Shutterstock

(Medical Xpress)—A Yale study has identified the underlying genetic basis of combined hyperlipidemia, as well as a treatment that may normalize the condition. The study appears in Cell Metabolism.

Combined is characterized by high plasma levels of triglycerides and LDL cholesterol. The disorder is a major risk factor for atherosclerosis of the coronary artery, , and other small and large arteries, leading to heart attack, stroke and limb ischemia.

Until now, very little has been known about the underlying mechanism of combined hyperlipidemia, and no single gene has been clearly linked to the disorder. The Yale researchers focused on the LRP6 gene and the effect of its mutation in mice. The mutation, which was first identified in humans with early onset and combined hyperlipidemia, causes a cascade of events in diverse signaling pathways that results in abnormally elevated levels of LDL and triglycerides.

In this study the investigators found that the abnormality in the Wnt signaling pathway affects the function of a transcription factor widely known for its association with diabetes and elevated . They further found that rescuing this pathway normalizes the expression of enzymes regulating plasma lipids and restores normal LDL and triglyceride levels.

A number of studies had previously shown direct or indirect association between Wnt signaling pathway and its coreceptor LRP6, and hyperlipidemia in humans. "Our finding basically establishes the link between them, and most importantly demonstrates that the hyperlipidemia can be rescued by normalization of this pathway," said senior author Arya Mani of the Yale Cardiovascular Research Center.

"Our study opens the way for potential development of novel therapeutics for treating hyperlipidemia, and a favorable outcome for coronary artery disease or survival," she added.

Explore further: Experts recommend screening adults for hypertriglyceridemia every five years

More information: Gwang-woong Go, Roshni Srivastava, Antonio Hernandez-Ono, Gyoungok Gang, Stephen B. Smith, Carmen J. Booth, Henry N. Ginsberg, Arya Mani. "The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue." Cell Metabolism, Volume 19, Issue 2, 209-220, 4 February 2014. 10.1016/j.cmet.2013.11.023

Related Stories

Recommended for you

How our cells use mother's and father's genes

September 28, 2016

Researchers at Karolinska Institutet and Ludwig Institute for Cancer Research have characterized how and to what degree our cells utilize the gene copies inherited from our mother and father differently. At a basic level ...

Questions, concerns about 'three-parent' baby

September 28, 2016

The surprise announcement that a healthy baby boy was born from a new technique mixing the DNA of two women and a man raises as many questions—scientific and ethical—as it settles, experts said Wednesday.

Regulatory RNA essential to DNA damage response

September 26, 2016

Stanford researchers have found that a tumor suppressor known as p53 is stabilized by a regulatory RNA molecule called DINO. The interaction helps a cell respond to DNA damage and may play a role in cancer development and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.