Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
    • Podcast
  • Press Release
  • Media Coverage
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Menu
  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
    • Podcast
  • Press Release
  • Media Coverage
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Home » Predicting the Severity of Cardiomyopathy via Genetic Modifiers
Disease Discoveries

Predicting the Severity of Cardiomyopathy via Genetic Modifiers

By Melissa RohmanMar 1, 2021
Share
Facebook Twitter Email
Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine, was senior author of the study published in Circulation.

A team of Northwestern Medicine investigators have identified specific genetic regions that regulate the expression of genes associated with inherited cardiomyopathy which may be able to predict overall disease severity, according to findings published in Circulation.

The study, led by Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine, has the potential to help guide the development of novel therapeutic approaches and help clinicians develop more personalized treatment plans for patients.

Inherited and non-inherited forms of cardiomyopathy — when the heart is unable to effectively deliver blood to the body — have similar outcomes, including arrhythmia and heart failure. The challenge, however, is determining whether someone has inherited cardiomyopathy because its symptoms present similarly to those of non-inherited cardiomyopathy.

Inherited cardiomyopathy, specifically, is associated with mutations in cardiomyopathy-related genes that, for some patients, can cause severe and early onset heart failure. These mutations are controlled by genetic modifiers, or mutations in various regions of the genome that influence how the primary genetic mutation produces a specific phenotype. When the heart fails, it undergoes a specific pattern of gene expression changes and these changes include expressing developmental forms of genes.

“With an increase in whole-genome sequencing and genetic data that is now available to clinicians, the goal is to use genetic information to predict which patients will have more severe and less severe disease,” said Anthony Gacita, a seventh-year student in the Medical Scientist Training Program (MSTP) and lead author of the study.

In the current study, investigators compared epigenomic profiles of human heart tissue samples and stem cell-derived cardiomyocytes to identify genetic regulators for cardiomyopathy-causing genes.

Anthony Gacita, a seventh-year student in the Medical Scientist Training Program, was lead author of the study.

One of the genes, MYH7, encodes the main molecular motor of the sarcomere, a fiber-like unit in heart cells that drives heart contraction. Mutations in MYH7 which directly change the protein are known to alter heart function and cause hypertrophic cardiomyopathy, a condition in which the heart becomes abnormally thick or “hypertrophied”. Other MYH7 mutations can cause the heart to enlarge and weaken.

The investigators identified a prominent genetic enhancer which regulates the expression of MYH7 and the neighboring gene, MYH6. Utilizing engineered heart tissues and CRIPSR gene editing, the team found that deleting this enhancer increased MYH6 expression and decreased MYH7 which increased the rate of heart tissue contraction. They also identified a DNA sequence change within a nearby enhancer region, called rs875908, and patients with this variant had faster cardiomyopathy progression.

“This is probably the first time in cardiomyopathy that a variant outside of the coding sequence has been associated with severity of phenotype,” Gacita said.

The findings may help guide the development of new therapeutic approaches for the disease, and the investigators’ integrated genomics approach could be used to study more than 150 known cardiomyopathy-related genes, according to Gacita. Whole-genome sequencing may also help inform clinicians of these genetic mutations earlier, allowing them to predict disease severity and provide more personalized treatment plans for patients.

In the future, McNally said the team hopes to use CRSIPR to increase or decrease cardiomyopathy gene expression by manipulating the noncoding parts of genes in an effort to decrease disease severity.

“We think this is a more tractable approach given the tools we have available now. New gene editing methods are being developed at a very rapid pace, and these newer modalities might have even more possibilities for genetic surgery to treat heart disease,” said McNally, who is also a Professor of Medicine in the Division of Cardiology and of Biochemistry and Molecular Genetics.

This work was supported by the National Institutes of Health grants HL128075, HL142187, HL141698 and the American Heart Association grant 18CDA34110460.

Cardiology Genetics Research
Share. Facebook Twitter Email

Related Posts

Hospitals Bound to Patient Safety Rules that Aren’t all Backed by Evidence

Jun 24, 2022

Identifying Protein Interactions that Promote Cancer Growth

Jun 24, 2022

Calcium Channel Blockers May Improve Chemotherapy Response

Jun 21, 2022

Comments are closed.

Latest News

Hospitals Bound to Patient Safety Rules that Aren’t all Backed by Evidence

Jun 24, 2022

Identifying Protein Interactions that Promote Cancer Growth

Jun 24, 2022

Combination Treatment May Improve Quality of Life in Kidney Cancer

Jun 23, 2022

Calcium Channel Blockers May Improve Chemotherapy Response

Jun 21, 2022

Expanded Role for Calcium Channels in T-Cells

Jun 17, 2022
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
20220607_Feinberg Campus_0070
20220607_Feinberg Campus_0066
20220607_Feinberg Campus_0054
Northwestern University 2022. Photo by Jim Prisching
20220607_Feinberg Campus_0077
20220607_Feinberg Campus_0063
20220607_Feinberg Campus_0111
20220607_Feinberg Campus_0083
20220607_Feinberg Campus_0018
20220607_Feinberg Campus_0023
20220607_Feinberg Campus_0072 (2)
20220607_Feinberg Campus_0120

Northwestern University logo

Northwestern University Feinberg School of Medicine

RSS Facebook Twitter LinkedIn Flickr YouTube Instagram
Copyright © 2022 Northwestern University
  • Contact Northwestern University
  • Disclaimer
  • Campus Emergency Information
  • Policy Statements

Type above and press Enter to search. Press Esc to cancel.