Hauck Ekkehard W, Hauptmann Arne, Schmelz Hans U, Bein Gregor, Weidner Wolfgang, Hackstein Holger
Department of Urology, Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany.
J Urol. 2003 Jan;169(1):369-72. doi: 10.1016/S0022-5347(05)64129-8.
The detection of increased expression of transforming growth factor beta-1 (TGF-beta1) in Peyronie's disease plaques and the possibility of initiating a Peyronie's disease-like condition by intratunical injection of a synthetic heptopeptide with TGF-beta-like activity in an animal model has provided evidence for the central role of this cytokine in the pathogenesis of this entity. Recently 2 defined single nucleotide polymorphisms in the coding region of the TGF-beta1 gene have been described that are associated with different levels of TGF-beta1 production. Based on these data we prospectively investigated the genetic association of distinct TGF-beta1 genotypes with Peyronie's disease.
DNA samples from 111 consecutive patients with idiopathic Peyronie's disease and 100 controls were genotyped for the 2 defined dimorphic single nucleotide polymorphisms T869C and G915C in the coding region of the TGF-beta1 gene using allele specific polymerase chain reaction.
We found an increased frequency of the homozygous genotype of the single nucleotide polymorphism G915C in patients with Peyronie's disease compared with healthy controls (89.2% versus 79%, p = 0.04). However, there were no significant differences in allele frequencies of the single nucleotide polymorphism T869C.
Experimental data from other investigators have shown that TGF-beta1 has an important role in the etiopathology of Peyronie's disease. Our results indicate that the homozygous wild type of the G915C single nucleotide polymorphism in the coding region of the TGF-beta1 gene, which was recently associated with elevated TGF-beta1 production and pulmonary fibrosis, may influence the predisposition to Peyronie's disease. However, it does not represent a major genetic risk factor.
在佩罗尼氏病斑块中检测到转化生长因子β-1（TGF-β1）表达增加，以及在动物模型中通过阴茎海绵体内注射具有TGF-β样活性的合成七肽引发类似佩罗尼氏病状况的可能性，为这种细胞因子在该疾病发病机制中的核心作用提供了证据。最近，已描述了TGF-β1基因编码区的2种明确的单核苷酸多态性，它们与不同水平的TGF-β1产生相关。基于这些数据，我们前瞻性地研究了不同TGF-β1基因型与佩罗尼氏病的遗传关联。
使用等位基因特异性聚合酶链反应，对111例连续的特发性佩罗尼氏病患者和100例对照的DNA样本进行TGF-β1基因编码区2种明确的双态单核苷酸多态性T869C和G915C的基因分型。
与健康对照相比，我们发现佩罗尼氏病患者中，单核苷酸多态性G915C的纯合基因型频率增加（89.2%对79%，p = 0.04）。然而，单核苷酸多态性T869C的等位基因频率没有显著差异。
其他研究者的实验数据表明，TGF-β1在佩罗尼氏病的病因学中起重要作用。我们的结果表明，TGF-β1基因编码区的G915C单核苷酸多态性的纯合野生型，最近与TGF-β1产生增加和肺纤维化相关，可能影响患佩罗尼氏病的易感性。然而，它并不代表主要的遗传危险因素。
