Jakobsson J, Palonek E, Lorentzon M, Ohlsson C, Rane A, Ekström L
1Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Pharmacogenomics J. 2007 Aug;7(4):282-9. doi: 10.1038/sj.tpj.6500419. Epub 2006 Sep 19.
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.
雄激素代谢酶的基因变异对于识别和表征很重要，因为它们可能影响前列腺癌风险并有助于阐明该疾病的病因。人类5型17β-羟类固醇脱氢酶（AKR1C3）在前列腺中高度表达，在雄激素的形成和代谢中起主要作用。我们在AKR1C3基因中鉴定出五个新的多态性。其中一个位于外显子2的A>G替换导致Glu77Gly变化，在白种人中出现频率为4.8%，而在东方人中完全不存在。有趣的是，携带Gly77等位基因的受试者血清睾酮水平显著较低。启动子A>G多态性与报告构建体中启动子活性的显著改变相关，但与睾酮水平的任何变化均无关。总之，Glu77Gly多态性与血清中较低的睾酮水平相关。
