The CAG repeat polymorphism in the androgen receptor gene is associated with HDL-cholesterol but not with coronary atherosclerosis or myocardial infarction.
BACKGROUND
Age-adjusted morbidity and mortality rates from coronary heart disease (CHD) are higher in men than in women. Androgens are suspected to be responsible for the male disadvantage. The genomic effect of androgens is mediated by the androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of repeats is inversely related to the transcriptional activity of the AR on target genes.


METHODS
We investigated the association of this CAG repeat polymorphism with CHD and myocardial infarction (MI) in 2 independent case-control studies involving 544 Caucasian men.


RESULTS
The number of CAG repeats in the AR gene correlated significantly with HDL-cholesterol (HDL-C) in controls (r = 0.21; P = 0.015). This effect was independent of triglycerides, body mass index, alcohol intake, smoking, and age in a multiple regression model (R(2) = 50%). Despite decreased HDL-C, lower CAG repeat numbers were not associated with increased risk for CHD (odds ratio = 0.82; 95% confidence interval, 0.50-1.36; P = 0.44) or MI in carriers of AR genes with lower CAG repeat numbers (odds ratio = 0.72; 95% confidence interval, 0.37-1.39; P = 0.33).


CONCLUSIONS
Shorter, more androgenic AR alleles with fewer CAG repeats are associated with lower HDL-C, but not with an increased risk for CHD or MI, which argues against a detrimental androgen effect on cardiovascular risk under physiologic conditions.
Hersberger
Martin
M
Institute of Clinical Chemistry, University Hospital, Zurich, Switzerland. hmr@ikc.unizh.ch
Muntwyler
Jörg
J
Funke
Harald
H
Marti-Jaun
Jacqueline
J
Schulte
Helmut
H
Assmann
Gerd
G
Lüscher
Thomas F
TF
von Eckardstein
Arnold
A
D000368:Aged; D000728:Androgens / Q000502:physiology; D001161:Arteriosclerosis / Q000235:genetics*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics*; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
D000728:Androgens; D008076:Cholesterol, HDL; D011944:Receptors, Androgen