Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Researchers Discover Underlying Genetics, Marker for Stroke, Cardiovascular Disease

Published: Saturday, March 22, 2014
Last Updated: Friday, March 21, 2014
Bookmark and Share
NIH-funded findings point to new potential strategies for disease prevention, treatment.

Scientists studying the genomes of nearly 5,000 people have pinpointed a genetic variant tied to an increased risk for stroke, and have also uncovered new details about an important metabolic pathway that plays a major role in several common diseases.

Together, their findings may provide new clues to underlying genetic and biochemical influences in the development of stroke and cardiovascular disease, and may also help lead to new treatment strategies.

"Our findings have the potential to identify new targets in the prevention and treatment of stroke, cardiovascular disease and many other common diseases," said Stephen R. Williams, Ph.D., a postdoctoral fellow at the University of Virginia Cardiovascular Research Center and the University of Virginia Center for Public Health Genomics, Charlottesville.

Dr. Williams, Michele Sale, Ph.D., associate professor of medicine, Brad Worrall, M.D., professor of neurology and public health sciences, all at the University of Virginia, and their team reported their findings March 20, 2014 in PLoS Genetics. The investigators were supported by the National Human Genome Research Institute (NHGRI) Genomics and Randomized Trials Network (GARNET) program (https://www.genome.gov/27541119).

Stroke is the fourth leading cause of death and a major cause of adult disability in this country, yet its underlying genetics have been difficult to understand. Numerous genetic and environmental factors can contribute to a person having a stroke. "Our goals were to break down the risk factors for stroke," Dr. Williams said.

The researchers focused on one particular biochemical pathway called the folate one-carbon metabolism (FOCM) pathway. They knew that abnormally high blood levels of the amino acid homocysteine are associated with an increased risk of common diseases such as stroke, cardiovascular disease and dementia.

Homocysteine is a breakdown product of methionine, which is part of the FOCM pathway. The same pathway can affect many important cellular processes, including the methylation of proteins, DNA and RNA. DNA methylation is a mechanism that cells use to control which genes are turned on and off, and when.

But clinical trials of homocysteine-lowering therapies have not prevented disease, and the genetics underlying high homocysteine levels - and methionine metabolism gone awry - are not well defined.

Dr. Williams and his colleagues conducted genome-wide association studies of participants from two large long-term projects: the Vitamin Intervention for Stroke Prevention (VISP), a trial looking at ways to prevent a second ischemic stroke, and the Framingham Heart Study (FHS), which has followed the cardiovascular health and disease in a general population for decades. They also measured methionine metabolism - the ability to convert methionine to homocysteine - in both groups. In all, they studied 2,100 VISP participants and 2,710 FHS subjects.

In a genome-wide association study, researchers scan the genome to identify specific genomic variants associated with a disease. In this case, the scientists were trying to identify variants associated with a trait - the ability to metabolize methionine into homocysteine.

Investigators identified variants in five genes in the FOCM pathway that were associated with differences in a person's ability to convert methionine to homocysteine. They found that among the five genes, one - the ALDH1L1 gene - was also strongly associated with stroke in the Framingham study. When the gene is not working properly, it has been associated with a breakdown in a normal cellular process called programmed cell death, and cancer cell survival.

They also made important discoveries about the methionine-homocysteine process. "GNMT produces a protein that converts methionine to homocysteine. Of the five genes that we identified, it was the one most significantly associated with this process," Dr. Williams said. "The analyses suggest that differences in GNMT are the major drivers behind the differences in methionine metabolism in humans."

"It's striking that the genes are in the same pathway, so we know that the genomic variants affecting that pathway contribute to the variability in disease and risk that we're seeing," he said. "We may have found how genetic information controls the regulation of GNMT."

The group determined that the five genes accounted for 6 percent of the difference in individuals' ability to process methionine into homocysteine among those in the VISP trial. The genes also accounted for 13 percent of the difference in those participants in the FHS, a remarkable result given the complex nature of methionine metabolism and its impact on cerebrovascular risk. In many complex diseases, genomic variants often account for less than 5 percent of such differences.

"This is a great example of the kinds of successful research efforts coming out of the GARNET program," said program director Ebony Madden, Ph.D. "GARNET scientists aim to identify variants that affect treatment response by doing association studies in randomized trials. These results show that variants in genes are associated with the differences in homocysteine levels in individuals."

The association of the ALDH1L1 gene variant with stroke is just one example of how the findings may potentially lead to new prevention efforts, and help develop new targets for treating stroke and heart disease, Dr. Williams said.

"As genome sequencing becomes more widespread, clinicians may be able to determine if a person's risk for abnormally high levels of homocysteine is elevated," he said. "Changes could be made to an individual's diet because of a greater risk for stroke and cardiovascular disease."

The investigators plan to study the other four genes in the pathway to try to better understand their potential roles in stroke and cardiovascular disease risk.


Further Information

Join For Free

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 3,000+ scientific posters on ePosters
  • More Than 4,500+ 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 TechnologyNetworks.com 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

Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Thursday, May 05, 2016
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
Wednesday, April 27, 2016
Factors Influencing Influenza Vaccine Effectiveness Uncovered
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests.
Thursday, April 21, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Serotonin Transporter Structure Revealed
Researchers determined the 3-D structure of the serotonin transporter and visualized how two common antidepressants interact with the protein.
Wednesday, April 20, 2016
Improving Flu Vaccine Effectiveness
NIH study finds factors that may influence influenza vaccine effectiveness.
Wednesday, April 20, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Migration Creates Cancer Cell Vulnerabilities
Scientists found that migration can damage cancer cells’ nuclei and DNA, requiring repairs for their survival. The results may open new avenues for targeting metastatic cancer.
Wednesday, April 13, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
NIH Awards Grants to Explore Vaccine Adjuvants
NIH awards six grants to explore how combination adjuvants improve vaccines.
Wednesday, April 06, 2016
Children With Cushing Syndrome May Have Higher Suicide Risk
Researchers at NIH have found that depression, anxiety and suicidal thoughts increase after treatment.
Wednesday, March 30, 2016
Experimental Vaccine Protects Against Dengue Virus
An experimental dengue vaccine protected all the volunteers who received it from infection with a live dengue virus.
Wednesday, March 30, 2016
Couples’ Pre-Pregnancy Caffeine Consumption Linked to Miscarriage Risk
Researchers at NIH have found daily multivitamin before and after conception greatly reduces miscarriage risk.
Friday, March 25, 2016
Study Finds Mindfulness Meditation Offers Relief For Low-Back Pain
Researchers at NIH have found that the MBSR and CBT may prove more effective than usual treatment in alleviating chronic low-back pain.
Wednesday, March 23, 2016
3-D Technology Enriches Human Nerve Cells For Transplant to Brain
This platform is expected to make transplantation of neurons a viable treatment for a broad range of human neurodegenerative disorders.
Friday, March 18, 2016
Scientific News
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Faster, Cheaper Way to Produce New Antibiotics
A novel way of synthesising a promising new antibiotic has been identified by scientists at the University of Bristol.
Process Contaminants in Vegetable Oils and Foods
Glycerol-based process contaminants found in palm oil, but also in other vegetable oils, margarines and some processed foods, raise potential health concerns for average consumers of these foods in all young age groups, and for high consumers in all age groups.
Improving Natural Killer Cancer Therapy
Vanderbilt University researchers discover transcription factor critical for NK cell expansion. Findings could lead to increased therapeutic efficacy.
Molecular Mechanism For Generating Specific Antibody Responses Discovered
Study could spur more ways to treat autoimmune disease, develop accurate vaccines.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
It’s Now Easier To Go With The Flow
Rice University tool simplifies comparison of flow cytometry data for laboratories.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
Genetic Variant May Help Explain Why Labradors Are Prone To Obesity
A genetic variation associated with obesity and appetite in Labrador retrievers – the UK and US’s favourite dog breed – has been identified by scientists at the University of Cambridge. The finding may explain why Labrador retrievers are more likely to become obese than dogs of other breeds.
Scroll Up
Scroll Down
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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!