Study Background

What is Hypertension?

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Recruitment Procedures

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Sibling pairs

Recruitment for the sibling pair study was initiated in late 1996. The aim was to recruit 1500 white European families based upon affected sibling pairs in order to map genes causing high blood pressure. (Demographics of the collected rescource)

At the out-set six recruitment centres were established and standard operating procedures in phenotyping, genetic counselling and genotyping were set up to ensure consistency between the sites.

All subjects participated as volunteers and were recruited via hypertension registers from the MRC General Practice Framework and Scottish hypertension clinics.

Inclusion criteria:

White European, British origin (up to level of grand-parental ancestry).

Men and women aged between 18-85 years with known hypertension.

The age of diagnosis of hypertension for the proband had to be less than 50 years and the sibling less than or equal to 60 years.

Both affected siblings in each family had to have blood pressure recordings of 150/100mmHg using 1 reading, or 145/95mmHg, mean of 3 readings whilst seated.

Both affected siblings had to meet blood pressure and age of onset criteria to be included in the study.

Exclusion criteria:

Affected individuals who consumed more than 21 units of alcohol per week.

Obese individuals defined as a BMI of 30 Kg/m2 or greater.

Diabetes (these may represent a different phenotype).

Individuals with intrinsic renal disease.

Individuals with a history of secondary hypertension, or co-existing illness, which could confound accurate phenotyping.

Questionnaire information:

Socio-economic, personal medical history, genealogy, family history of cardiovascular disease and medication were all recorded.

Phenotypic measurements:

On treatment blood pressure recordings using the Omron HEM-705CP, portable, semi-automated oscillometric device (Omron Healthcare).

24 hour ambulatory blood pressure recordings (Spacelabs, Model 90207).

Anthropometric measurements (waist-hip ratio, skin fold thickness and body mass index).

A 12-lead electrocardiogram (ECG) was performed.

Each participant was offered an echocardiogram.

Samples, biochemistry and urinary analysis:

Venous blood was collected for biochemical analysis, DNA extraction and peripheral blood lymphocyte preparation.

Blood glucose concentration, total cholesterol, triglycerides, g-GT, urate, and electrolytes were measured at a single central chemical pathology lab in Glasgow (Members of National Quality Assurance Scheme, CPA accredited).

A 24-hour urine sample was also collected and from this 24-hour creatinine clearance, urinary electrolytes and albumin/creatinine ratio were measured.

Data protection and databases:

A unique family identification number was given to each individual and subsequently blood, urine and DNA samples were stored using this identifier.

Computerised records of all samples conformed to the Data Protection Act.

All phenotypic/biochemical and genetic data is stored in a password protected MySQL relational database. To ensure accuracy and data quality control we employed a double data entry system whereby 2 independently trained staff entered all the phenotypic information, a third person reconciled any inconsistencies. Entry of biochemical results and Minnesota coded ECGs was by direct electronic transfer.

The BRIGHT study sib pair recruitment was extremely successful and comprises 1708 families based upon sibling pairs.

Demographics of the sibling pair rescource