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Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany

(Requests for offprints should be addressed to A M Hillmer; Email: axel.hillmer{at}uni-bonn.de)

Genetic studies have reported association of a polyglycine-encoding GGN repeat in exon 1 of the androgen receptor (AR) gene with common human traits. The polyglycine tract is located in the transactivating domain of the AR protein, suggesting an effect of repeat length on receptor function. Here, we compare the functional characteristics of the two most common alleles (23 and 24 repeats) and two extreme alleles (10 and 27 repeats) in a reporter gene assay in HeLa cells. A correlation between the repeat length and AR activity was observed. This is attributable to both a higher protein concentration, determined by ELISA, and a higher per-protein activity of long repeat alleles. Interestingly, protein concentration does not correlate with transcript quantity, determined by real-time PCR assays, and no influence of repeat length on protein stability could be detected in translation inhibition assays. This may suggest that repeat length affects translation efficiency. In conclusion, our data provide evidence of functional differences between the two most common alleles of the AR GGN repeat, supporting its potential role in the development of human traits.

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