Cardiovascular Diseases
Conditions
Keywords
Healthy Volunteers, Genetic Risk Markers for Disease, Coronary Heart Disease, Coronary Artery Disease, Immune Response, Red Blood Cells, Inflammation
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.
Interventions
OTHERQuestionnaire
Medical history, demographics and lifestyle factors will be assessed by the participant.
Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.
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.
PROCEDUREVenepuncture (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
PROCEDUREVenepuncture (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
Sponsors
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United Kingdom
Outcome results
None listed