Prevalence of beta-2 adrenergic receptor (β2AR) polymorphisms in Malay population and relationship of these polymorphisms to a model assessing macrovascular endothelial function
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Date
2009
Authors
Nik Ibrahim, Dr Nik Nor Izah
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Abstract
Endothelial dysfunction has been shown to precede atherosclerosis. The assessment of
endothelial function allows early detection of atherosclerosis and may help in
preventive strategies. Recently, pulse wave analysis (PWA) combined with
pharmacological challenges has been shown to be a promising non invasive method of
assessing endothelium function. The pharmacological challenges involve
administrations of sublingual glyceryl trinitrate (GTN) as an endothelium-independent
vasodilator and inhaled salbutamol as an endothelium dependent vasodilator. The
response to salbutamol, a β2-agonist may be affected by genetic polymorphisms of Beta-
2 adrenergic receptor (β2AR). Beta-2 adrenergic receptor polymorphisms have been
implicated in the pathogenesis of many diseases as well as inter individual differences
in patients’ response to treatment mediated by β2AR.
The objectives of this thesis were to determine the prevalence of β2AR
polymorphisms in our population and to determine if these polymorphisms influence the
model used to assess macrovascular endothelial function using PWA.
Genotyping was done to detect 5 functionally important single nucleotide
polymorphisms (SNPs) of β2AR in 388 healthy Malay subjects. All SNPs were
simultaneously detected using the published method allele specific nested multiplex
polymerase chain reaction (PCR). Out of this, 298 subjects proceeded with clinical
measurement of macrovascular endothelial function. Augmentation index (AIx) and
carotid-femoral pulse wave velocity (PWV) recordings were taken at baseline, done
non-invasively using SphygmoCor. Subjects were then administered with 500 μg of
sublingual GTN followed by AIx and PWV recordings. After a wash-out period, 400
μg of inhaled salbutamol was given followed by AIx and PWV recordings. The
maximum changes in AIx and PWV after each pharmacological challenge were taken as
final measurements.
The frequencies of variant alleles Gly16, Glu27, Ile164, -20C and -47C were
47%, 6.8%, 0%, 30% and 9.3% respectively. In term of genotype frequencies, for
codons 16 and 27 the most common genotypes were Arg/Gly and Gln/Gln with
frequencies 81.4% and 87.1% respectively; for nucleotides -20 and -47 were TT with
frequencies 50% and 82.2% respectively; whereas at codon 164, 100% of the genotype
was Thr/Thr. No significant differences were noted in AIx after GTN and salbutamol in
all groups. Similarly, no significant differences were noted in PWV after GTN and
salbutamol in all groups.
In conclusion the prevalence of β2AR polymorphisms in Malays in our
population correspond to that reported in other Asian populations. Model used to assess
macrovascular endothelial function using PWA was not influenced by β2AR
polymorphisms.
Description
Master
Keywords
Medical science , Polymorphisms , Macrovascular endothelial