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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Other: Anthropometric measurements: height, weight, and body fat; Other: Blood pressure and heart rate; Other: Questionnaire; Procedure: Venepuncture (GMPR); Procedure: Venepuncture (SWAP70)

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB1 8RN
      • Department of Public Health and Primary Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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).

Description

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.

Additional exclusion criteria to be applied at the discretion/opinion of the CI/collaborator, based on the population of available volunteers for recall and the genetic variant of interest (e.g. allele frequency):

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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: Anthropometric measurements: height, weight, and body fat; Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.; 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.; Other: Questionnaire; Medical history, demographics and lifestyle factors will be assessed by the participant.; Procedure: 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
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: Anthropometric measurements: height, weight, and body fat; Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.; 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.; Other: Questionnaire; Medical history, demographics and lifestyle factors will be assessed by the participant.; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure (systolic and diastolic)	All study arms comparing results between genotypic groups.	At baseline
Heart rate	All study arms comparing results between genotypic groups.	At baseline

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: University of Cambridge
• Investigators: Principal Investigator: Dirk Paul, PhD, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Coronary Artery Disease; Healthy Volunteers; Immune Response; Red Blood Cells; Coronary Heart Disease; Genetic Risk Markers for Disease
• Additional Relevant MeSH Terms: Vascular Diseases; Pathologic Processes; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases; Inflammation; Coronary Artery Disease; Coronary Disease; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Circulatory and Respiratory Physiological Phenomena; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Enzymes; Enzymes and Coenzymes; Physical Examination; Vital Signs; Hemodynamics; Cardiovascular Physiological Phenomena; Oxidoreductases; Nitroreductases; Weights and Measures; Surveys and Questionnaires; Blood Specimen Collection; Blood Pressure; Heart Rate; GMP Reductase
• Other Study ID Numbers: GENBIO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant identifiable information is securely held, with restricted access, by the NIHR BioResource. Members of the research team carrying out the procedures will not be able to request the link to decode this information. Only the minimum required participant identifiable information (name and contact details) will be provided to the research team for the purpose of arranging study visits and completing the informed consent process. All research personnel will be sufficiently blinded of the genotype status of the healthy volunteers. All delegated research personnel that is responsible to conduct the data/statistical analysis will only analyse data that is anonymised of any patient identifiable data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No