Renko Outi, Savolainen Eeva-Riitta, Loikkanen Ildikó, Paavonen Timo K, Vaarala Markku H
Department of Pathology, University of Oulu, Oulu, Finland.
DNA Cell Biol. 2008 Feb;27(2):109-13. doi: 10.1089/dna.2007.0665.
The development of benign prostatic hyperplasia requires the presence of testicular androgens during prostate development, puberty, and ageing. We thus examined the association of three polymorphisms, namely, CYP3A5 6986A>G, CYP19A1 1531C>T, and androgen receptor (AR) gene CAG repeat length, which have previously been linked to the androgen pathway and with clinical characteristics of benign prostatic hyperplasia. Tissue samples from 262 consecutive prostate operations were used for genotyping. Prostate volumes and prostate-specific antigen values were collected from patient records. Linear regression analysis was performed to study the polymorphisms in an age-adjusted model. We did not find any association between the CYP3A5 6986A>G polymorphism and clinical characteristics of benign prostatic hyperplasia. Further, the previously published CYP19A1 1531C>T polymorphism association with an enlarged prostate could not be confirmed with this material. However, we detected an association between short AR gene CAG repeat length and a small prostate volume, which confirms a previous finding in the Finnish population. The data presented suggest a negligible role for the CYP3A5 6986A>G polymorphism in benign prostate enlargement in the Finnish population. However, the results presented do provide further evidence for potentially different genetic mechanisms behind benign prostatic hyperplasia in Finnish and other Caucasian populations. This is based on the conflicting results for AR gene CAG repeat length associations with benign prostatic hyperplasia found in published works.
良性前列腺增生的发展需要在前列腺发育、青春期及衰老过程中存在睾丸雄激素。因此,我们研究了三种多态性的关联,即CYP3A5 6986A>G、CYP19A1 1531C>T以及雄激素受体(AR)基因CAG重复序列长度,这些多态性先前已与雄激素途径以及良性前列腺增生的临床特征相关联。来自262例连续前列腺手术的组织样本用于基因分型。从患者记录中收集前列腺体积和前列腺特异性抗原值。在年龄校正模型中进行线性回归分析以研究这些多态性。我们未发现CYP3A5 6986A>G多态性与良性前列腺增生的临床特征之间存在任何关联。此外,用该材料无法证实先前发表的CYP19A1 1531C>T多态性与前列腺增大之间的关联。然而,我们检测到AR基因CAG重复序列长度短与前列腺体积小之间存在关联,这证实了芬兰人群先前的一项发现。所呈现的数据表明CYP3A5 6986A>G多态性在芬兰人群良性前列腺增大中的作用可忽略不计。然而,所呈现的结果确实为芬兰和其他白种人群良性前列腺增生背后潜在不同的遗传机制提供了进一步证据。这是基于已发表研究中AR基因CAG重复序列长度与良性前列腺增生关联的相互矛盾的结果。