1. ¹Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
2. ²Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Gothenburg University, Göteborg, Sweden

Correspondence: Dr L Ekström, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, C1.68, SE-141 86 Stockholm, Sweden. E-mail: lena.ekstrom@ki.se

Received 21 April 2006; Revised 13 July 2006; Accepted 24 July 2006; Published online 19 September 2006.

Abstract

Genetic variation in the androgen metabolizing enzymes is important to identify and feature as they may influence the risk of prostate cancer and help clarify the etiology of the disease. Human 17-hydroxysteroid dehydrogenase type 5 (AKR1C3) is highly expressed in the prostate gland and plays a major role in the formation and metabolism of androgens. We identified five novel polymorphisms in the AKR1C3 gene. One of those an A>G substitution in exon 2 that confers a Glu77Gly change occurred in 4.8% in Caucasians but was completely absent in Orientals. Interestingly, the testosterone level in serum was significantly lower in subjects with the Gly77 allele. A promoter A>G polymorphism was associated with significantly altered promoter activity in reporter constructs, but was not associated with any change in testosterone levels. In conclusion, the Glu77Gly polymorphism is associated with lower testosterone levels in serum.