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

NCT04931498 | Active Not Recruiting

• 1 other identifier: GENBIO
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Diseases

Keywords

Healthy Volunteers; Genetic Risk Markers for Disease; Coronary Heart Disease; Coronary Artery Disease; Immune Response; Red Blood Cells; Inflammation

Outcome Measures

Primary Outcomes (6)

• Levels of GMPR protein in isolated erythrocytes

  GMPR-specific measurement to be assessed by mass spectrometry, comparing results between different GMPR genotypic groups.

  At baseline

• Levels of SWAP70 protein in immune cell subsets

  SWAP70-specific measurement to be assessed by flow cytometry, comparing results between SWAP70 genotypic groups.

  At baseline

• Proportion of immune cell types as measured using flow cytometric analysis

  SWAP70-specific measurement to be assessed by flow cytometry (e.g. lymphoid and myeloid cell markers), comparing results between SWAP70 genotypic groups.

  At baseline

• Levels of genes/transcripts in immune cell subsets

  SWAP70-specific measurement to be assessed by RNA sequencing, comparing results between SWAP70 genotypic groups.

  At baseline

• Concentration of immunoglobulin isotypes in plasma

  SWAP70-specific measurement to be assessed by immunoglobulin isotype (IgM, IgG, IgA and IgE) analysis, comparing results SWAP70 genotypic groups.

  At baseline

• Phagocytosis by monocytes as measured by colorimetric analysis (optical density)

  SWAP70-specific measurement to be assessed by phagocytosis assays, comparing results between SWAP70 genotypic groups. The phagocytosis assay uses pre-labelled Zymosan particles as a pathogen for triggering phagocytosis. The engulfed Zymosan particles react with a specific substrate to produce a signal that can be detected by colorimetric analysis.

  At baseline

Secondary Outcomes (2)

• Blood pressure (systolic and diastolic)

  At baseline

• Heart rate

  At baseline

Study Arms (2)

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.

Other: Questionnaire; Other: Anthropometric measurements: height, weight, and body fat; Other: Blood pressure and heart rate; Procedure: Venepuncture (GMPR)

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).

Other: Questionnaire; Other: Anthropometric measurements: height, weight, and body fat; Other: Blood pressure and heart rate; Procedure: Venepuncture (SWAP70)

Interventions

Questionnaire OTHER

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

GMPR sub-study; SWAP70 sub-study

Anthropometric measurements: height, weight, and body fat OTHER

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

GMPR sub-study; SWAP70 sub-study

Blood pressure and heart rate 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.

GMPR sub-study; SWAP70 sub-study

Venepuncture (GMPR) 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

GMPR sub-study

Venepuncture (SWAP70) 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

SWAP70 sub-study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will only recruit healthy volunteers who have previously consented to being contacted for future studies by the NIHR Cambridge BioResource, which is a panel of around 20,000 volunteers, both with and without health conditions, who are willing to be approached to participate in research studies investigating the links between genes, the environment, health and disease. Volunteers who join the NIHR BioResource have donated their DNA via a blood or saliva sample that is used together with other information, such as sex and ethnicity, to match them to specific research studies. Participants for this study are identified by having the appropriate genetic sequence in one of the two genetic loci we are investigating (SWAP70, GMPR).

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• University of Cambridge: collaborator

Study Sites (1)

Department of Public Health and Primary Care

Cambridge, Cambridgeshire, CB1 8RN, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Disease; Coronary Artery Disease; Inflammation

Interventions

Surveys and Questionnaires; Weights and Measures; Blood Pressure; Heart Rate; Blood Specimen Collection; GMP Reductase

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Nitroreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes

Study Officials

• Dirk Paul, PhD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: June 18, 2021
• Study Start: March 1, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)