Dilated cardiomyopathy (DCM) is caused by a combination of genetic susceptibility and environmental factors. Cathepsin B affects the pathogenesis of DCM; however, its molecular mechanism is still unclear. In this study, we examined the association of rare CTSB variants with the occurrence of DCM. This case-control study involved 394 participants: 142 patients with DCM and 252 healthy controls. DNA was extracted from the peripheral leukocytes of all participants, and CTSB variants were analyzed and identified using polymerase chain reaction amplification. Functional analysis was performed using the dual-luciferase reporter assay, and the ability of genetic CTSB variants to bind to transcription factors (TFs) was analyzed and validated using the electrophoretic mobility shift assay (EMSA). Two single-nucleotide polymorphisms (SNPs) were identified in the study population. One SNP, g.4803 T > C (rs1293312), was more common in patients with DCM. A second SNP, g.4954 T > A (rs942670850), was identified in two patients with DCM. Both SNPs significantly enhanced the transcriptional activity of CTSB promoters. An analysis using the TRANSFAC database revealed that these SNPs affect TF binding, which was confirmed using the EMSA. Our results demonstrate that within the CTSB promoter, the genetic variants g.4803T>C (rs1293312) and g.4954 T > A (rs942670850) are rare risk factors for DCM development.

中文翻译：

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CTSB启动子多态性与扩张型心肌病功能的相关性分析。

扩张型心肌病 (DCM) 是由遗传易感性和环境因素共同引起的。组织蛋白酶 B 影响 DCM 的发病机制；然而，其分子机制仍不清楚。在这项研究中，我们检查了罕见 CTSB 变异与 DCM 发生的关联。这项病例对照研究涉及 394 名参与者：142 名 DCM 患者和 252 名健康对照者。从所有参与者的外周血白细胞中提取 DNA，并使用聚合酶链反应扩增法分析和鉴定 CTSB 变异体。使用双荧光素酶报告分析进行功能分析，并使用电泳迁移率变动分析 (EMSA) 分析和验证遗传 CTSB 变体与转录因子 (TF) 结合的能力。在研究人群中发现了两个单核苷酸多态性 (SNP)。一个 SNP，g.4803 T > C (rs1293312)，在 DCM 患者中更常见。在两名 DCM 患者中发现了第二个 SNP，g.4954 T > A (rs942670850)。两个 SNP 都显着增强了 CTSB 启动子的转录活性。使用 TRANSFAC 数据库的分析表明，这些 SNP 会影响 TF 结合，这已使用 EMSA 得到证实。我们的结果表明，在 CTSB 启动子中，遗传变异 g.4803T>C (rs1293312) 和 g.4954 T > A (rs942670850) 是 DCM 发展的罕见风险因素。两个 SNP 都显着增强了 CTSB 启动子的转录活性。使用 TRANSFAC 数据库的分析表明，这些 SNP 会影响 TF 结合，这已使用 EMSA 得到证实。我们的结果表明，在 CTSB 启动子中，遗传变异 g.4803T>C (rs1293312) 和 g.4954 T > A (rs942670850) 是 DCM 发展的罕见风险因素。两个 SNP 都显着增强了 CTSB 启动子的转录活性。使用 TRANSFAC 数据库的分析表明，这些 SNP 会影响 TF 结合，这已使用 EMSA 得到证实。我们的结果表明，在 CTSB 启动子中，遗传变异 g.4803T>C (rs1293312) 和 g.4954 T > A (rs942670850) 是 DCM 发展的罕见风险因素。