BRIEF REPORT Frequent Finding of the Androgen Receptor A645D Variant in Normal Population

Results:The A645D variant was found in three men from the general population (1.0%). These men did not differ regarding testosterone or LH concentrations, compared with the rest of this population. In addition, two men with prostate cancer (2.3%) and one infertile man (1.0%) presented with the mutation. No statistical differences in frequency were noted between the study groups, and none of these individuals had any genital malformations. All men who presented with the mutation carried an extraordinarily short GGN repeat of 10 base triplets in combination with long CAG repeats of 26–28 (average 27.3). In contrast, men with GGN10, but CAG less than 26 did not have the A645D mutation. A single-nucleotide polymorphism analysis revealed that the A645D variant has emerged from the most common haplogroup in our population. Conclusions: We conclude that the A645D mutation, which is present in 1% of the general Swedish population, is linked to GGN10 and long CAG repeats. Its effect on androgen receptor function is currently unknown. (J Clin Endocrinol Metab 91: 3228–3231, 2006)