Genetic variation may lead to early cardiovascular disease

January 3, 2009

Researchers from Duke University Medical Center have identified a variation in a particular gene that increases susceptibility to early coronary artery disease. For years, scientists have known that the devastating, early-onset form of the disease was inherited, but they knew little about the gene(s) responsible until now. The results are published January 2 in the open-access journal PLoS Genetics.

In a previous study, a region on chromosome 7 was linked to coronary artery disease (CAD). More recently, the researchers focused on identifying the gene in this region that confers risk of early-onset CAD and identified it as the neuropeptide Y (NPY) gene. NPY is one of the most plentiful and important proteins in the body and is a neurotransmitter related to the control of appetite and feeding behavior, among other functions.

The current research, led by Svati Shah and Elizabeth Hauser, found evidence for six related variations in the NPY gene that show evidence of transmission from generation to generation and association across a population of early-onset CAD patients.

The researchers evaluated 1,000 families for CAD or evidence of a true heart attack, as part of the GENECARD study put together by the Duke University Cardiology Consortium. An independent, nonfamilial study used a collection of samples of nearly everyone who had an angiogram at Duke since 2001. Co-authors William Kraus and Christopher Granger founded this repository, called CATHGEN, which is now nearing 10,000 subjects. The nonfamilial work showed a strong relationship between the NPY genetic variants associated with coronary disease.

The genetic results were even stronger in patients with onset of CAD before the age of 37. "We showed a strong age effect," said Hauser. "If one has the NPY gene variants in one of two copies (from mother and father), then you may develop coronary disease earlier."

"These young patients are a vulnerable population on whom CAD has a significant long-term impact, but they are particularly hard to identify and therefore to initiate preventive therapies for," Shah said. "These and other genetic findings may help us in the future to identify these patients prior to development of CAD or their first heart attack."

The group further examined NPY levels in blood and found that, among the six NPY variants, there is a single-nucleotide change of the DNA code on the NPY promoter region of the gene - the part of the gene that turns it on and off. This single-letter change was associated with higher NPY levels, suggesting that this was the functional change that predisposes a person to early onset CAD.

"If you had 1 or 2 copies of this mutant version of the gene, there could be a change in NPY level," Shah said. "The concept is that small changes over time can promote atherosclerosis (hardening of the arteries) at a very young age."

Mouse studies subsequently confirmed that the NPY pathway promotes atherosclerosis. The next step may be to examine the children of the people who were studied. Studying the heterogeneity among individuals with early-onset disease - overweight versus normal weight families, for example - will also be important.

Citation: Shah SH, Freedman NJ, Zhang L, Crosslin DR, Stone DH, et al. (2009) Neuropeptide Y Gene Polymorphisms Confer Risk of Early-Onset Atherosclerosis. PLoS Genet 5(1): e1000318. doi:10.1371/journal.pgen.1000318
http://dx.plos.org … pgen.1000318

Source: Public Library of Science


Rank 5 /5 (3 votes)
Relevant PhysicsForums posts

More news stories

Overeating may double risk of memory loss

New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study was released today and will be ...

Medicine & Health / Neuroscience

created 35 minutes ago | popularity not rated yet | comments 0 | with audio podcast

Injured boomers beware: Know when to see doctor

(AP) -- It happened to nurse Jane Byron years after an in-line skating fall, business owner Haralee Weintraub while doing "men's" push-ups, and avid cyclist Gene Wilberg while lifting a heavy box.

Medicine & Health / Health

created 5 hours ago | popularity 5 / 5 (1) | comments 0

Starve a virus, feed a cure? Findings show how some cells protect themselves against HIV

A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online ...

Medicine & Health / Research

created 4 hours ago | popularity 5 / 5 (1) | comments 0 | with audio podcast

FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice

Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...

Medicine & Health / Neuroscience

created Feb 09, 2012 | popularity 4.9 / 5 (57) | comments 15 | with audio podcast

Green tea found to reduce disability in the elderly

(Medical Xpress) -- A lot of research has been done over the past several years looking into the health benefits of green tea. As a result, scientists have found that regular consumption of the beverage leads ...

Medicine & Health / Health

created Feb 07, 2012 | popularity 4.4 / 5 (15) | comments 10 | with audio podcast report


Google might launch Drive for cloud storage soon

(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...

Scientists discover molecular secrets of 2,000-year-old Chinese herbal remedy

For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, ...

New method to examine batteries -- MRI from the inside

There is an ever-increasing need for advanced batteries for portable electronics, such as phones, cameras, and music players, but also to power electric vehicles and to facilitate the distribution and storage of energy derived ...

Lab study raises questions over nano-particle impact

Tests involving chickens have raised questions about the impact on health from engineered nano-particles, the ultra-fine grains commonly used in drugs and processed foods, scientists said on Sunday.

A mitosis mystery solved: How chromosomes align perfectly in a dividing cell

Although the process of mitotic cell division has been studied intensely for more than 50 years, Whitehead Institute researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric ...

Researchers find extensive RNA editing in human transcriptome

In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demons ...