|
ANDROGEN RECEPTOR CAG POLYMORPHISM AND HEART DISEASE
Alevizaki, M
Endocrine Unit, Dept. of Clinical Therapeutics, Athens University
School of Medicine, Alexandra Hospital, 51 Ionnou
Theologou, 15773, Athens, Greece
The role of androgens in the pathogenesis of coronary artery disease
(CAD) remains controversial. It has been suggested
that hormonal parameters may be of importance for
the predisposition of men to CAD. Studies measuring
androgen levels have shown contradictory results,
however circulating hormones may not reflect exactly
the biological action at the tissue level. The effects
of androgens are exerted via the androgen receptor
(AR), located on chromosome X. The AR has a polymorphic
region in exon 1 with a varying number of a polyglutamines
encoded by a stretch of CAG repeats. The length of
the CAG repeats of the AR affects the transactivation
function of the receptor, and shows an inverse correlation
with androgenic action. A few studies have examined
possible associations of the length of the AR CAG
repeat with cardiovascular risk factors as well as
with the severity of CAD in males. It has been found
that both the endothelium dependent vasodilatation
is impaired and the HDL levels are lower in men carrying
the shorter repeats, associated with increased androgen
sensitivity. We examined a population undergoing coronary
anghiography: Men with short AR CAG repeat length
had a higher prevalence of extensive coronary artery
stenosis compared to men with longer AR repeat length.
In this study we found that men with longer AR gene
CAG repeat lengths also had higher estradiol levels.
It is possible that this finding indirectly reflects
the increased testosterone levels that are expected
in the case of the polymorphism associated with mild
"resistance". In conclusion the shorter CAG repeat
of the AR, is associated with more severe CAD, which
suggests a role for the sensitivity to androgens in
the increased frequency of CAD in males. In addition,
a protective role of endogenous estrogen, which is
higher in the longAR subgroup, can contribute to the
observed difference.
|
