The androgen receptor gene polyglycine repeat polymorphism is associated with memory performance in healthy Chinese...

Cognitive functions such as memory are quantitative traits in human, and have both genetic and environmental influences. Testosterone has been implicated in the modulation of memory function. Therefore, genetic variation which influences testosterone signaling may modulate memory function. The principal receptor for testosterone is the androgen receptor, the gene for which maps to the X chromosome. In the present study, we hypothesized that common variation in two functional polymorphisms in the androgen receptor gene, the polyglutamine (CAG) and/or polyglycine (GGN) repeats, would influence memory function in healthy subjects. Variation in length of either repeat modulates the function of the AR gene, either by changing the amount of protein produced, by altering transactivation of the receptor or by producing toxic polyglycine or polyglutamine fragments. In order to test this hypothesis, we analyzed 449 healthy Chinese individuals. CAG repeats were not associated with memory performance. However we observed a significant association between GGN repeats and Immediate Logical Memory (chi(2)=23.6, d.f.=7, p=0.001) and Delayed Logical Memory (chi(2)=16.3, d.f.=7, p=0.022). The association of GGN repeats with Immediate Logical Memory remained significant after 6000 permutation corrections (p=0.013). There was also a sex difference, as association between GGN repeats and memory was observed only in females (p=0.002 for Immediate and p=0.014 for Delayed Logical Memory), but not in males (p=0.31 and 0.83, respectively). We conclude that functional variation of the androgen receptor gene is able to modulate memory function in women.