Trinucleotide (CAG) repeat polymorphism of the androgen receptor gene in human disease

Abstract

The androgen receptor (AR) is a member of the superfamily of steroid hormone receptors. The AR gene contains a polymorphic region comprising variable number of CAG repeats which encodes glutamine residues in its first exon. In this thesis, the role of the polymorphic CAG repeat stretch in the activity of the AR was investigated in three diseases/conditions: male infertility, PCOS in women, and prostate cancer. Subsequently, the mechanism by which the different CAG length confers different transactivation activity to the AR was investigated in cell culture studies by using human promoters. In conclusion, the results from the three different studies in humans indicated that short CAG tracts were associated with high levels of androgen action leading to PCOS in females and high levels of PSA in males, and conversely long CAG tracts were associated with low androgen receptor activity leading to male infertility.