A novel polymorphism in the 17beta-hydroxysteroid dehydrogenase type 5 (aldo-keto reductase 1C3) gene is associated with lower serum testosterone levels in caucasian men.

• 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 17beta-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.

Nyckelord

17-Hydroxysteroid Dehydrogenases

genetics

metabolism

3-Hydroxysteroid Dehydrogenases

genetics

metabolism

Asian Continental Ancestry Group

Blotting

Western

Cell Line

Tumor

Databases

Nucleic Acid

European Continental Ancestry Group

genetics

Exons

Expressed Sequence Tags

Gene Frequency

Genes

Reporter

Humans

Hydroxyprostaglandin Dehydrogenases

genetics

metabolism

Introns

Luciferases

Male

Polymorphism

Single Nucleotide

Testosterone

blood

Transfection

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)