Sabeti Akbar-Abad Mahboobeh, Majidpour Mahdi, Sargazi Saman, Ghasemi Marzieh, Saravani Ramin
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Reprod Sci. 2025 Apr;32(4):1166-1179. doi: 10.1007/s43032-025-01806-w. Epub 2025 Mar 5.
Polycystic ovary syndrome (PCOS) occurs in women of reproductive age, impairing reproductive and metabolic processes. Variations in the cathepsin B (CTSB) gene can influence the disease prognosis by changing the activity, stability, or expression. These single-nucleotide polymorphisms (SNPs) can affect critical cellular functions like the deposition of extracellular matrix, inflammation, and tissue repair, leading to the development of multifactorial diseases. Our study aims to investigate the association between PCOS risk and CTSB SNPs. In this case-control study, 150 PCOS cases and 150 healthy women were enrolled. Genotyping was conducted using the PCR-RFLP method. Different computational databases were used to predict the impact of variations on the splicing sites. Regarding rs12898, the codominant homozygous (GG vs. AA) and recessive (GG vs. AA + AG) inheritance models reduced PCOS risk by 72% and 71%, respectively. PCOS risk was increased by 2.81, 2.94, 1.62, and 2.20 folds in the codominant (TT vs. CC), recessive (TT vs. CC + CT), T vs. C (rs8898), and T vs. C (rs3779659) modes, respectively. Based on haplotype analysis, ATC and ACT haplotypes significantly enhance PCOS risk by 1.57 and 3.34 folds, respectively. Furthermore, the interaction analysis indicated that AG/TT/CC and AA/TT/CC genotype combinations strongly correlated with high PCOS risks by 2.59 and 4.20 folds, respectively. The CTSB rs12898 G > A and rs8898 C > T can potentially create or disrupt binding sites for several splicing factors. CTSB rs12898, rs8898, and rs3779659 SNPs were associated with PCOS risk in our population. Larger sample sizes will be necessary to confirm these findings and investigate other potential causal factors involved in PCOS etiology.
多囊卵巢综合征（PCOS）发生于育龄女性，会损害生殖和代谢过程。组织蛋白酶B（CTSB）基因的变异可通过改变其活性、稳定性或表达来影响疾病预后。这些单核苷酸多态性（SNP）可影响关键的细胞功能，如细胞外基质沉积、炎症和组织修复，从而导致多因素疾病的发生。我们的研究旨在调查PCOS风险与CTSB SNP之间的关联。在这项病例对照研究中，纳入了150例PCOS患者和150名健康女性。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行基因分型。使用不同的计算数据库来预测变异对剪接位点的影响。对于rs12898，共显性纯合子（GG与AA）和隐性（GG与AA + AG）遗传模型分别使PCOS风险降低了72%和71%。在共显性（TT与CC）、隐性（TT与CC + CT）、T与C（rs8898）以及T与C（rs3779659）模式下，PCOS风险分别增加了2.81倍、2.94倍、1.62倍和2.20倍。基于单倍型分析，ATC和ACT单倍型分别使PCOS风险显著增加了1.57倍和3.34倍。此外，交互作用分析表明，AG/TT/CC和AA/TT/CC基因型组合分别与高PCOS风险密切相关，风险分别增加了2.59倍和4.20倍。CTSB rs12898 G>A和rs8898 C>T可能会潜在地创建或破坏几种剪接因子的结合位点。在我们的研究人群中，CTSB rs12898、rs8898和rs3779659 SNP与PCOS风险相关。需要更大的样本量来证实这些发现，并研究PCOS病因中涉及的其他潜在因果因素。
