Corporate Banner
Satellite Banner
Metabolomics & Lipidomics
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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

Newly Discovered Cells Restore Liver Damage in Mice Without Cancer Risk
The liver is unique among organs in its ability to regenerate after being damaged. Exactly how it repairs itself remained a mystery until recently, when researchers supported by the NIH discovered a type of cell in mice essential to the process
Monday, August 17, 2015
Study Finds Cutting Dietary Fat Reduces Body Fat More than Cutting Carbs
In a recent study, restricting dietary fat led to body fat loss at a rate 68 percent higher than cutting the same number of carbohydrate calories when adults with obesity ate strictly controlled diets.
Friday, August 14, 2015
Inappropriate Medical Food Use in Managing Patients with a Type of Metabolic Disorder
Researchers have proposed that there is a need for more rigorous clinical study of dietary management practices for patients with IEMs, including any associated long-term side effects, which may in turn result in the need to reformulate some medical foods.
Friday, August 14, 2015
Ease of Weight Loss Influenced by Individual Biology
NIH study finds varied responses to calorie restriction in obese adults.
Tuesday, May 12, 2015
Molecule Hijacks Enzyme To Boost Alcohol Metabolism
Study could lead to treatments for people with impaired acetaldehyde metabolism.
Tuesday, February 24, 2015
Metabolomics: Taking Aim at Diabetic Kidney Failure
Krolewski and his Joslin colleagues search for better ways of predicting which diabetic people are at risk for ESRD.
Saturday, February 08, 2014
Speeding Validation of Disease Targets
NIH, industry and non-profits join forces to develop new treatments earlier, beginning with Alzheimer’s, type 2 diabetes, and autoimmune disorders.
Tuesday, February 04, 2014
Study to Examine if Vitamin D Prevents Diabetes
NIH-funded research will test the much-touted vitamin in people with prediabetes.
Monday, October 21, 2013
NIH Researchers Find Diabetes Drug Extends Health and Lifespan in Mice
Study was published in the July 30, 2013 issue of Nature Communications.
Thursday, September 05, 2013
Endocannabinoids Trigger Inflammation That Leads to Diabetes
NIH scientists identify possible treatment target for type 2 diabetes.
Thursday, August 22, 2013
Possible Treatment Target for Type 2 Diabetes Identified
Researchers at the NIH have clarified in rodent and test tube experiments the role that inflammation plays in type 2 diabetes, revealing a possible molecular target for treating the disease.
Tuesday, August 20, 2013
Diabetes Drug Extends Health and Lifespan in Mice
Long-term treatment with the type 2 diabetes drug metformin improves health and longevity of male mice when started at middle age.
Wednesday, July 31, 2013
Scientists Identify Molecular Link between Metabolism and Breast Cancer
A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer.
Wednesday, February 06, 2013
NIH Announces New Program in Metabolomics
The National Institutes of Health will invest $14.3 million this year with the potential to invest more than $51.4 million over five years.
Friday, September 21, 2012
U.S. and India Sign Joint Statement
The statement provides greater opportunities for collaborative projects ranging from research to identify genes for diabetes to bettering public health efforts to manage and treat of diabetes.
Friday, June 22, 2012
Scientific News
How Cell Growth Triggers Cell Division
Researchers in Jan Skotheim's lab have discovered a previously unknown mechanism that controls how large cells grow, an insight that could one day provide insight into attacking diseases such as cancer.
Metabolomic Platform Reveals Fundamental Flaw in Common Lab Technology
A new study led by scientists at The Scripps Research Institute (TSRI) shows that a technology used in thousands of laboratories, called gas chromatography mass spectrometry (GC-MS), fundamentally alters the samples it analyzes.
Newly Identified Biochemical Pathway Could Be Target for Insulin Control
Researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.
Dirty,Crusty Meals Fit for (Long-Dormant) Microbes
Researchers apply the latest analytical techniques to further our understanding of desert biocrusts.
CSI -- On The Metabolite's Trail
Bioinformaticians at the University of Jena make the most efficient search engine for molecular structures available online.
Developing a Breathalyzer-Type Low Blood Sugar Warning Device For Diabetes
A multidisciplinary team of researchers at Indiana University-Purdue University Indianapolis has been awarded a $738,000 National Science Foundation grant to develop a breathalyzer-type device to detect the onset of hypoglycemia, or low blood sugar episodes, in people with diabetes.
Identifying The 'Dimmer Switch' Of Diabetes
University of Alberta research gives new insight into what causes Type 2 diabetes.
10 to 1: Bugs Win in NASA study
Bugs are winning out, and that's a good thing according to NASA's Human Research Program.
MYC Oncogene Disrupts Cancers Rhythm
Findings inform time-dependent treatment for reducing side effects and increasing effectiveness of cancer medications.
Keeping Gut Bacteria in Balance Could Help Delay Age-related Diseases
A new study suggests that analyzing intestinal bacteria could be a promising way to predict health outcomes as we age.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos