Objective

1.6 Objective

To date, investigations on the genetic basis of hypertension have largely focused on candidate genes of the renin angiotensin system [44]. The sympathetic nervous system functions as a second important regulator of blood pressure via alterations in vascular responsiveness, renin release, renal sodium handling and cardiac output. In this respect, adrenergic receptors might be important to increase total peripheral resistance and hence blood pressure.

As mentioned before, several mutations of the β₂ adrenergic receptor gene have already been characterised, some of which show distinct functional changes (see chapter 5).

This thesis tried to test whether variants of the β₂ adrenoceptor gene operating individually or in combination influence blood pressure level as a quantitative trait and hypertension as a qualitative trait. This was undertaken in an association study in two different populations, a large black Afro-Caribbean one (St. Vincent and the Grenadines, Chapter 3) as well as within a homogenous, representative white European population recruited with the primary aim of prospective investigation of environmental and genetic factors for cardiovascular disease (Caerphilly Prospective Heart Study, Chapter 4).

The Caerphilly Study was done in the framework of a big interdisciplinary cooperation with St. Bartholomew’s Hospital, London. The author’s work included DNA resampling, complete genotyping and statistics, as well as DNA extraction of additional blood samples.

Figure 1.5:

Proposed model for insertion of the β₂ adrenergic receptor in the cell membrane. The model is based on hydropathicity analysis of the human β₂ receptor according to the methods of Kyte and Doolittle [114]. The standard one-letter code for amino acid residues is used. Also noted are the potential sites of N-linked glycosylation. Shown is the receptor that is termed wild-type [111].

[next] [prev] [prev-tail] [front] [up]