The Genetic, Protein, and Lipid Basis of Variation in Cholesterol Efflux

NCT ID: NCT04061018

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 59 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2025-05-31

Brief Summary

The rationale of this research is that deep phenotyping of individuals at the extremes of cholesterol efflux will identify key determinants of efflux that are potential novel therapeutic targets to prevent or reverse Atherosclerotic Cardiovascular Disease (ASCVD). The investigators propose to carry out the objective by studying participants at extreme low and high cholesterol efflux identified from the investigator's study in the population-based Dallas Heart Study by accomplishing the following aims: 1) determine the heritability of and genomic factors associated with cholesterol efflux by establishing a family pedigree of extreme low and high efflux and sequencing candidate genes involved in HDL metabolism; and 2) identify the protein and lipid signature of extreme low and high cholesterol efflux in a sex- and ethnicity-specific manner using mass spectroscopy and ELISA in FPLC-derived fractions. The investigators expect to identify genetic variants and sex- and ethnicity-specific combinations of proteins and lipids in participants with extreme low and high efflux that may lead to novel ways to modulate efflux. This proposal leverages a well-phenotyped population-based study to characterize the gene-protein-lipid signature of 1) extremes of cholesterol efflux in a sex- and ethnicity-specific manner. Successful completion of these aims will have immediate and direct impact on the use of cholesterol efflux as a clinically relevant biomarker of therapeutic benefit and are necessary for the clinical development of appropriate new targets for manipulation of the key atheroprotective function of cholesterol efflux to reduce ASCVD.

Detailed Description

The mechanisms that underlie variation in cholesterol efflux are unknown. There is a critical need to identify factors that regulate cholesterol efflux to effectively advance the clinical development of cholesterol efflux as both a risk prediction marker and as a target of therapy. The investigator's long-term goal is to determine whether modulating cholesterol efflux prevents or reverses cardiovascular disease. The overall objective of this study is to systematically create a family pedigree and biobank repository of blood and DNA from participants from the Dallas Heart Study with extreme low or high cholesterol efflux, with the specific aims of : 1) determining the heritability of and genomic factors associated with cholesterol efflux, and 2) identifying the protein and lipid signature of extreme low and high cholesterol efflux in a sex- and ethnicity-specific manner. The investigator's central hypothesis is that a combination of genetic variation in lipid transporters as well as proteins and lipids will be most strongly correlated with variation in efflux.

DHS probands and their relatives (parents, siblings, adult children, grandparents, aunts/uncles, cousins) with extreme low or high cholesterol efflux will be recruited to establish a prospective family pedigree cohort and understand the heritability of extreme cholesterol efflux. Investigators will collect the following information from all participants: demographics, health history, lifestyle measures, and medications. Blood will be collected on-site by venipuncture and plasma, serum, and cells will be stored at -80o Celsius. All efflux measurements will be completed in the investigator's laboratory.

Conditions

Lipid Metabolism Disorders

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

High Cholesterol Efflux

Dallas Heart Study participants who are above the sex and ethnicity specific 90th % of cholesterol efflux

No interventions assigned to this group

Low Cholesterol Efflux

Dallas Heart Study participants who are below the sex and ethnicity specific 10th % of cholesterol efflux

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Dallas Heart Study (DHS) Participants who are above or below the sex- and ethnicity-specific 10th and 90th% of cholesterol efflux.
• Family members of the DHS participants are also eligible

Exclusion Criteria

• HIV
• Cancer
• Autoimmune diseases
• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Anand Rohatgi

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anand Rohatgi, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwetsern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

1R01HL136724-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU 042016-020

Identifier Type: -

Identifier Source: org_study_id