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

NHS Foundation Trust

Status: Active, not recruiting

Conditions: Cardiovascular Diseases

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

Study type: Observational

Funder types: Other

Identifiers

NCT04931498

GENBIO

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

100 participants in 2 patient groups

GMPR sub-study

Description:

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.

Treatment:

Procedure: Venepuncture (GMPR)

Other: Anthropometric measurements: height, weight, and body fat

Other: Questionnaire

Other: Blood pressure and heart rate

SWAP70 sub-study

Description:

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).

Treatment:

Other: Anthropometric measurements: height, weight, and body fat

Procedure: Venepuncture (SWAP70)

Other: Questionnaire

Other: Blood pressure and heart rate