Azzouzi Abdel-Rahmene, Cochand-Priollet Beatrix, Mangin Philippe, Fournier Georges, Berthon Philippe, Latil Alain, Cussenot Olivier
CeRePP-EA3104, Universite Paris VII, Genopole, 4 rue Pierre Fontaine, Evry F-91000, France.
Eur J Endocrinol. 2002 Oct;147(4):479-84. doi: 10.1530/eje.0.1470479.
Benign prostatic hyperplasia (BPH) is the most common benign tumour in ageing men. While the etiopathology remains unsolved, a disruption in the endocrine/autocrine-paracrine prostatic homeostasis, involving steroid hormones, contributes to the pathogenesis of BPH. DNA polymorphisms in genes involved in hormone synthesis, signalling and metabolism may, therefore, be responsible for these changes. We have evaluated the correlation between specific genotypes in androgen- and oestrogen-regulating genes (AR, SRD5A2, CYP17 and CYP19), and age-related prostatic changes.
We have tested genetic susceptibility to morphological and pathological criteria in 195 French Caucasians, using allelic variants for candidate genes involved in androgen/oestrogen prostatic activity: androgen receptor (CAG repeats), 5alpha-reductase type 2 (TA repeats, V89L and A49T mutations), A2 variant of the 17alpha-hydroxylase (CYP17) and the simple tandem repeat polymorphism (STRP) aromatase (CYP19) polymorphisms.
The A2 variant of 17alpha-hydroxylase (CYP17) and allele 191 of STRP aromatase (CYP19) showed an opposite effect on age-related prostate hyperplasia: CYP17 being associated with increased risk of prostate enlargement and CYP19 with reduced risk. The 5alpha-reductase type II variants studied did not show links with prostate hyperplasia. The androgen receptor gene CAG repeat length showed a low correlation with the increase of prostate weight, suggesting some effect on age-related prostate growth.
These results suggested that common variants of the CYP17 gene are associated with prostate enlargement and therefore may increase the risk of development of BPH in this population, while infrequent variants of the aromatase gene (CYP19) could be of a protective nature.
良性前列腺增生（BPH）是老年男性中最常见的良性肿瘤。虽然其病因病理学仍未解决，但涉及类固醇激素的内分泌/自分泌-旁分泌前列腺内环境稳态的破坏，促成了BPH的发病机制。因此，参与激素合成、信号传导和代谢的基因中的DNA多态性可能是这些变化的原因。我们评估了雄激素和雌激素调节基因（AR、SRD5A2、CYP17和CYP19）中的特定基因型与年龄相关的前列腺变化之间的相关性。
我们在195名法国白种人中，使用参与雄激素/雌激素前列腺活性的候选基因的等位基因变体，测试了对形态学和病理学标准的遗传易感性：雄激素受体（CAG重复序列）、2型5α-还原酶（TA重复序列、V89L和A49T突变）、17α-羟化酶（CYP17）的A2变体以及芳香化酶（CYP19）多态性的简单串联重复多态性（STRP）。
17α-羟化酶（CYP17）的A2变体和STRP芳香化酶（CYP19）的等位基因191对年龄相关的前列腺增生表现出相反的影响：CYP17与前列腺增大风险增加相关，而CYP19与风险降低相关。所研究的2型5α-还原酶变体与前列腺增生没有关联。雄激素受体基因CAG重复序列长度与前列腺重量增加的相关性较低，表明对年龄相关的前列腺生长有一定影响。
这些结果表明，CYP17基因的常见变体与前列腺增大相关，因此可能增加该人群中BPH发生的风险，而芳香化酶基因（CYP19）的罕见变体可能具有保护作用。
