Zole Egija, Baumanis Edgars, Freimane Lauma, Dāle Rolands, Leiše Andrejs, Lietuvietis Vilnis, Ranka Renāte
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, k-1, LV-1067 Riga, Latvia.
Clinic of Urology and Oncologic Urology, Riga East University Hospital, Hipokrata Street 2, LV-1038 Riga, Latvia.
Biomedicines. 2024 Oct 15;12(10):2349. doi: 10.3390/biomedicines12102349.
Benign prostatic hyperplasia (BPH) is a growing issue due to an ageing population. Our study investigated the possible associations between BPH and ageing hallmarks, including the telomere length (TL) and mitochondrial genome copy number (mtDNA CN), along with genetic variations in the gene and mtDNA.
Prostate tissue samples were obtained from 32 patients with BPH, together with 30 blood samples. As a healthy control group, age-matching blood DNA samples were used. For the comparison of mtDNA sequence data, 50 DNA samples of the general Latvian population were used. The full mtDNA genome was analyzed by using Next-Generation Sequencing (NGS), the gene by Sanger sequencing, and the mtDNA copy number (mtDNA CN) and telomere length (TL) byqPCR assay.
The results showed that in BPH patients, telomeres in the prostate tissue were significantly longer than in blood cells, while the TL in blood cells of the healthy controls was the shortest. Also, the mtDNA amount in the prostate tissue of BPH patients was significantly greater in comparison with blood cells, and controls had the smallest mtDNA CN. We did not find any mutations in the gene that could be linked to BPH; however, in mtDNA, we found several unique mutations and heteroplasmic changes, as well as genetic changes that have been previously associated with prostate cancer.
In conclusion, prolonged telomeres and changes in the mtDNA amount might be involved in the molecular mechanisms of BPH. Some of the heteroplasmic or homoplasmic mtDNA variants might also contribute to the development of BPH. Additional studies are needed to substantiate these findings.
由于人口老龄化，良性前列腺增生（BPH）问题日益突出。我们的研究调查了BPH与衰老标志之间的可能关联，包括端粒长度（TL）和线粒体基因组拷贝数（mtDNA CN），以及该基因和mtDNA中的遗传变异。
从32例BPH患者中获取前列腺组织样本，以及30份血液样本。作为健康对照组，使用年龄匹配的血液DNA样本。为了比较mtDNA序列数据，使用了50份拉脱维亚普通人群的DNA样本。通过下一代测序（NGS）分析完整的mtDNA基因组，通过桑格测序分析该基因，通过qPCR测定法分析mtDNA拷贝数（mtDNA CN）和端粒长度（TL）。
结果显示，在BPH患者中，前列腺组织中的端粒明显长于血细胞中的端粒，而健康对照组血细胞中的TL最短。此外，BPH患者前列腺组织中的mtDNA量与血细胞相比明显更大，而对照组的mtDNA CN最小。我们在该基因中未发现任何可与BPH相关联的突变；然而，在mtDNA中，我们发现了几个独特的突变和异质性变化，以及先前与前列腺癌相关的遗传变化。
总之，端粒延长和mtDNA量的变化可能参与了BPH的分子机制。一些异质性或同质性mtDNA变异也可能促成BPH的发展。需要进一步的研究来证实这些发现。
