Precision Medicine Approach to Heart Transplantation: Identification of Patients at Risk for Poor Transplant Outcome

Tech ID: col000953

 

Introduction

According to the United Network Organ Sharing (UNOS) national database, the majority of patients that received heart transplants in the United States or are waiting to receive one, belong to either European American (EA) or African American (AA) ethnicity. In year 2016 to date alone, 61% of the total 5980 heart transplant patients are European American and 25% are African American.  It is seen that transplantation outcomes, however, are dismal in African American compared to European American recipients. While one-year survival rate of EA is comparable to that of AA (87.6% vs 86.2% respectively), the survival rate of AA sharply decreases as compared to EA with time, with five-year survival rate corresponding to 73.3% for EA and 64% for AA.

This ethnic disparity after heart transplantation has persisted despite improvement in our knowledge of heart transplant science, immunosuppression options and treatment regimens. Discoveries in immunosuppressive medications have certainly improved heart transplant outcomes over the decades. However, to date nothing has been developed to screen genetic risk in the populations of interest. As such, there exists a great need for methods that can categorize heart transplant patients based on the risk for poor transplant outcome, and methods that can prognose and/or treat such patients.

 

Technology Description

Dr. Bernice Coleman and colleagues at Cedars-Sinai Medical Center conducted a GWAS in AA and EA heart transplant recipients to develop a genetic risk score (GRS) as a predictor of ethnic survival after heart transplantation. Based on their understanding that a higher prevalence of rejection mediating pro-inflammatory polymorphisms in immune response genes may be the basis of increased risk of death in AA heart transplant recipients, the inventors investigated the impact of inflammatory single nucleotide polymorphisms (SNPs) on development of GRS, and explored clinical phenotype predictors of survival within the genetic risk categories and ethnic groups. A total of 257 heart transplant recipients (AA 53 and EA 204) were analyzed in this study. It was observed that significant inflammatory SNPs independently associated with AA (9) and EA (12) distinguished between patients at high genetic risk or low genetic risk for poor survival. Based on the GRS, subjects were classified into high risk groups determined by the GRS being greater than the median score and low risk groups being GRS less than median score.

The use of a GRS as a measure of vulnerability to risk stratify high risk patients for poor outcomes after heart transplantation will be highly useful for patient care. Our data has identified candidate SNPs offering an approach to exploring the disparity among ethnic groups where appropriate intervention may be possible. These SNPs may identify patients who require a different immunosuppressive regimen.

 

Advantages/Novelty

Novel method to screen genetic risk of poor outcomes of heart transplantation in African American and European American patients.

 

Applications

• Individualized treatment plan to heart transplant patients based on risk for poor transplant outcome.

• Diagnose patients with heart disease early enough to tailor their treatment to possibly prevent heart failure at a later stage.

• Identify newborns, children, and young adults that may be at a risk of heart failure with the intent of delivering preventive interventions that could impact environmental epigenetic factors.

 

Intellectual Property

• US provisional patent application filed.

 

Patent Information:
Category(s):
Diagnostic
For Information, Contact:
Wenyue Du
Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Bernice Coleman
Mark Goodarzi
Jon Kobashigawa
Keywords:
Cardiovascular