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

Underlying Genetics and Marker For Stroke Discovered

Published: Friday, March 21, 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.

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.

In addition to NHGRI, the research was supported by funds from the National Heart, Lung and Blood Institute, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging and the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine.

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

Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Beth Israel Cardiology Team Awarded $3 Million by NIH
Work will help predict outcomes in patients with heart disease.
Friday, September 18, 2015
NIH Awards Nearly $35 Million to Research Natural Products
Innovative Research Centers Program investigates botanical dietary supplements and other natural products.
Thursday, September 10, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Tuesday, August 04, 2015
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Monday, August 03, 2015
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Possible Treatment for Lethal Pediatric Brain Cancer
NIH-funded preclinical study suggests epigenetic drugs may be used to treat leading cause of pediatric brain cancer death.
Tuesday, May 05, 2015
HIV can Spread Early, Evolve in Patients' Brains
Findings add urgency to screening, treatment - NIH-funded study.
Saturday, March 28, 2015
Test Reliably Detects Inherited Immune Deficiency in Newborns
NIH-supported study suggests that early diagnosis of severe combined immunodeficiency leads to high survival rates.
Thursday, August 21, 2014
NIH Names New Clinical Sites in Undiagnosed Diseases Network
Four-year, $43 million initiative engages broad expertise in study of mystery conditions.
Wednesday, July 02, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Potential Persistent Tuberculosis Treatment
Researchers have discovered several first-in-class compounds that target hidden TB infections by attacking a critical process the bacteria use to survive in the hostile environment of the lungs.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
The Do’s and Don’ts of SPR Experiments
Surface Plasmon Resonance (SPR) is a technique that is becoming more widely used, particularly by anyone who wants to obtain accurate on (association) and off (dissociation) rates for biomolecular binding.
Long-Sought Protein Sensor for the ‘Sixth Sense’ Discovered
In a study led by scientists from The Scripps Research Institute (TSRI)the sensor protein for propioception has been identified.
New Anti-Malarial Drug Screening Model
University of South Florida researchers demonstrate novel chemogenomic profiling to identify drug targets for the most lethal strain of malaria.
Shedding Light on “Dark” Cellular Receptors
UNC and UCSF labs create a new research tool to find homes for two orphan cell-surface receptors, a crucial step toward finding better therapeutics and causes of drug side effects.
New, Better Test for Prostate Cancer
A study from Karolinska Institutet shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
Giant Molecules Inhibit Ebola Infection
European researchers have designed a "giant" molecule formed by thirteen fullerenes covered by carbohydrates which, by blocking this receptor, are able to inhibit the cell infection by an artificial ebola virus model.

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