Molecular Investigation of GENetic Factors in Cardiovascular and Immune-related Traits and Diseases Using a BIOresource of Healthy Volunteers (GENBIO)

NCT ID: NCT04931498

Last Updated: 2025-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-03-01

Study Completion Date

2026-09-30

Brief Summary

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The risk of cardiovascular disease is determined by the complex interplay between an individual's genetic make-up, lifestyle, and the environment. The researchers in this observational, cross-sectional, recall-by-genotype study are investigating two potential genetic risk factors; the SWAP70 gene is thought to play a role in the immune response modulating cardiovascular disease risk and the GMPR gene plays a role in red blood cell formation. The investigators hope to identify and characterise distinct molecular and cellular mechanisms underlying candidate functional variants identified in genetic studies of cardiovascular and immune-related human traits and diseases.

Healthy volunteers who are part of the NIHR BioResource and have already been genotyped will be invited to the study based on their genotype of the candidate functional variants of interest. Volunteers will attend a single study visit, during which they will complete procedures including a medical, demographic and lifestyle factors questionnaire; height, weight and body fat assessments; in addition to blood pressure/heart rate measurements. A minimally invasive procedure of a venepuncture will be performed to assess the primary objectives of the study.

The obtained data may (1) improve understanding of biological and disease mechanisms; (2) identify potential drug targets; and (3) improve insight into the therapeutic potential and limitations of existing and emerging therapies.

This study is funded by the UK Medical Research Council, British Heart Foundation and NIHR Cambridge Biomedical Research Centre.

Detailed Description

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Conditions

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Cardiovascular Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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GMPR sub-study

Study population will be split into five haplotypes based on a combination of rare and common variants at the GMPR locus. A total of 26 volunteers per genotypic group in a comparison between heterozygous and homozygous individuals will be tested.

Questionnaire

Intervention Type OTHER

Medical history, demographics and lifestyle factors will be assessed by the participant.

Anthropometric measurements: height, weight, and body fat

Intervention Type OTHER

Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Blood pressure and heart rate

Intervention Type OTHER

Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Venepuncture (GMPR)

Intervention Type PROCEDURE

A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests:

* Flow cytometry to quantify cell surface expression of key erythroid markers
* Proteomic analysis of isolated erythrocytes using mass spectrometry

SWAP70 sub-study

To assess genotype-specific effects on SWAP70 protein levels as well as coronary artery disease-related immune processes, we will recruit 50 volunteers stratified by variant genotype, i.e. major and minor homozygotes only (25 participants will be recruited to each group).

Questionnaire

Intervention Type OTHER

Medical history, demographics and lifestyle factors will be assessed by the participant.

Anthropometric measurements: height, weight, and body fat

Intervention Type OTHER

Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Blood pressure and heart rate

Intervention Type OTHER

Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Venepuncture (SWAP70)

Intervention Type PROCEDURE

A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests:

* Flow cytometry to quantify cell surface expression of key markers
* Fluorescence-Activated Cell Sorting (FACS) to assess B-cell receptor signalling and to isolate cell type-specific RNA for transcriptome analysis
* Immunoglobulin isotype titre analysis in plasma
* Isolation of monocytes for subsequent use in phagocytosis assays

Interventions

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Questionnaire

Medical history, demographics and lifestyle factors will be assessed by the participant.

Intervention Type OTHER

Anthropometric measurements: height, weight, and body fat

Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Intervention Type OTHER

Blood pressure and heart rate

Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Intervention Type OTHER

Venepuncture (GMPR)

A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests:

* Flow cytometry to quantify cell surface expression of key erythroid markers
* Proteomic analysis of isolated erythrocytes using mass spectrometry

Intervention Type PROCEDURE

Venepuncture (SWAP70)

A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests:

* Flow cytometry to quantify cell surface expression of key markers
* Fluorescence-Activated Cell Sorting (FACS) to assess B-cell receptor signalling and to isolate cell type-specific RNA for transcriptome analysis
* Immunoglobulin isotype titre analysis in plasma
* Isolation of monocytes for subsequent use in phagocytosis assays

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Have consented to be part of the NIHR BioResource;
* Are aged 18 years and above;
* Have given written informed consent to participate in the GENBIO study;
* Are carriers or non-carriers of the candidate functional genetic variant(s) of interest.

Exclusion Criteria

Have a chronic disease, including cardiovascular diseases, autoimmune diseases and cancer.


* Have a biological first-degree relatives (parents, brothers, sisters or children) who are suffering or have suffered from a disease/condition in the opinion of the CI/collaborator that, from a genetic standpoint, may affect the study validity;
* Are current regular smokers. Regular ex-smokers are suitable if they stopped smoking \>10 years ago (regular defined as 1 pack year in both instances);
* Have ≥3 alcoholic drinks per day;
* Have a diagnosis of hypertension, or history of consistently high blood pressure readings, e.g. \>140/90 mmHg;
* Have a diagnosis of hypercholesterolemia, or history of consistently high cholesterol levels, e.g. total cholesterol level \>6 mmol/l;
* Are obese (i.e. BMI \>30);
* Are unwilling to fast and not to consume products containing alcohol or caffeine 12 hours prior to procedures.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Cambridge

OTHER

Sponsor Role collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Dirk Paul

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dirk Paul, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Locations

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Department of Public Health and Primary Care

Cambridge, Cambridgeshire, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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GENBIO

Identifier Type: -

Identifier Source: org_study_id

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