Molecular Investigation of GENetic Factors in Cardiovascular and Immune-related Traits and Diseases Using a BIOresource of Healthy Volunteers (GENBIO)
- Conditions
- Cardiovascular Diseases
- Interventions
- Other: QuestionnaireOther: Blood pressure and heart rateProcedure: Venepuncture (GMPR)Procedure: Venepuncture (SWAP70)
- Registration Number
- NCT04931498
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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.
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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description GMPR sub-study Blood pressure and heart rate 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. SWAP70 sub-study Questionnaire 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). GMPR sub-study Questionnaire 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. SWAP70 sub-study Blood pressure and heart rate 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). GMPR sub-study Venepuncture (GMPR) 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. SWAP70 sub-study Venepuncture (SWAP70) 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).
- Primary Outcome Measures
Name Time Method Levels of genes/transcripts in immune cell subsets At baseline SWAP70-specific measurement to be assessed by RNA sequencing, comparing results between SWAP70 genotypic groups.
Concentration of immunoglobulin isotypes in plasma At baseline SWAP70-specific measurement to be assessed by immunoglobulin isotype (IgM, IgG, IgA and IgE) analysis, comparing results SWAP70 genotypic groups.
Phagocytosis by monocytes as measured by colorimetric analysis (optical density) At baseline 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.
Levels of GMPR protein in isolated erythrocytes At baseline GMPR-specific measurement to be assessed by mass spectrometry, comparing results between different GMPR genotypic groups.
Levels of SWAP70 protein in immune cell subsets At baseline SWAP70-specific measurement to be assessed by flow cytometry, comparing results between SWAP70 genotypic groups.
Proportion of immune cell types as measured using flow cytometric analysis At baseline SWAP70-specific measurement to be assessed by flow cytometry (e.g. lymphoid and myeloid cell markers), comparing results between SWAP70 genotypic groups.
- Secondary Outcome Measures
Name Time Method Heart rate At baseline All study arms comparing results between genotypic groups.
Blood pressure (systolic and diastolic) At baseline All study arms comparing results between genotypic groups.
Trial Locations
- Locations (1)
Department of Public Health and Primary Care
🇬🇧Cambridge, Cambridgeshire, United Kingdom