Cross, Deborah Jane
(2004)
β2-adrenoceptor gene polymorphisms and hypertension in African Trinidadians.
PhD thesis, University of Nottingham.
Abstract
Background
Essential hypertension remains a major risk factor for coronary heart disease (CHO) and stroke, and its prevalence is greater, more severe, occurs earlier, and is less well controlled among black individuals than among white individuals, at all ages after young adult hood (Comoni-Huntley et al, 1989).
In Caucasians, studies have shown that β2-adrenoceptor polymorphism accounts for the variability in the vascular responsiveness to the agonist isoprenaline (Cockcroft et al, 1994 and Lang et al, 1995). Individuals homozygous for Gln 27 β2-adrenoceptor showed reduced responses due to chronic down regulation of β2-adrenoceptor in the vasculature. Therefore, variability in response to isoprenaline was determined by β2-adrenoceptor gene polymorphism.
Aim and Objectives
This study investigated whether there is a relationship between the ArglGly16 and Gln/Glu 27 β2-adrenoceptor polymorphisms by examining whether the incidence of occurrence is prevalent in African Trinidadians. In addition, comparison data of vascular responses with arterial compliance using pulse wave analysis (PWA) was correlated. The study aimed to give evidence if these polymorphisms contributed fully or in part, to determine the disease severity, or response to therapy in hypertensive individuals. It also aimed to prove that PWA is a reliable and therapeutic tool, in diagnosing and treating blood pressure, as reliance on brachial artery recording of blood pressure, alone, is becoming a poor indicator and predictor of risk.
Methods
The study genotyped 408 African Trinidadian subjects for the β2-adrenoceptor polymorphism and used the technique of applanation tonometry to analyse the central pulse wave, generating information on arterial compliance, left ventricular function and coronary perfusion. Blood pressure was measured in triplicate using a semiautomatic blood pressure meter after 15 minutes of supine rest and bloods lipids assessed using a validated portable lipid cartridge. This was achieved by subjects attending a nurse-led cardiovascular risk clinic.
Results
There is no significant association between the Arg-Glyl6 polymorphism and the Gln-Glu27 polymorphism and hypertension in African Trinidadians. Interestingly, the appearance of the Glu27 polymorphism was very uncommon in African Trinidadians and this is constant with findings by Candy et al, 2000.
Conclusion
There is no difference in the frequency of β2-polymorphisms between normotensive and hypertensive African Trinidadians, and are unlikely to be a contributing factor for essential hypertension. Therefore, hypertension would indicate that it is polygenic with complex gene to gene and gene environmental interactions, through multiple, indirect and intermediate phenotypes and interactions.
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