Identification and pathological significance of variants in the promoter region of ACTC1 gene in congenital ventricular septal defect

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-08-21 DOI:10.1016/j.gene.2025.149733

Zi-Fei Zheng , Huan-Xin Chen , Jia-Le Qi , Zhuo Chen , Qin Yang , Guo-Wei He

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Abstract

Ventricular septal defect (VSD) is one of the most common congenital heart diseases, but the role of variants at the ACTC1 gene promoter region in VSD is unclear. We investigated variants in the promoter region of ACTC1 gene in 627 subjects (309 sporadic VSD patients and 318 healthy controls) by Sanger sequencing and 6 variants including 1 novel heterozygous variant [g.5163 T > A] were identified. Of the 6 variants, 3 were found only in VSD patients. In mouse cardiomyocytes (HL-1), the transcriptional activity of the ACTC1 gene promoter was significantly changed by the variants (p < 0.05). Electrophoretic mobility shift assay results and JASPAR database analysis indicated that these variants may affect the transcription of the ACTC1 gene by influencing the binding ability of transcription factors, thus potentially contributing to the formation of VSD. This study provides a new perspective for the genetic and molecular mechanism of variants of the promoter region of ACTC1 gene in the pathogenesis of VSD.

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先天性室间隔缺损ACTC1基因启动子区变异的鉴定及病理意义

室间隔缺损（Ventricular septal defect， VSD）是最常见的先天性心脏病之一，但ACTC1基因启动子区变异在VSD中的作用尚不清楚。我们通过Sanger测序研究了627名受试者（309名散发性VSD患者和318名健康对照者）的ACTC1基因启动子区域的变异和6个变异，其中包括1个新的杂合变异[g.5163]T > A]。6个变异中，3个仅在VSD患者中发现。在小鼠心肌细胞（HL-1）中，这些变异显著改变了ACTC1基因启动子的转录活性（p < 0.05）。电泳迁移量转移实验结果和JASPAR数据库分析表明，这些变异可能通过影响转录因子的结合能力来影响ACTC1基因的转录，从而可能促进VSD的形成。本研究为研究ACTC1基因启动子区变异在VSD发病中的遗传和分子机制提供了新的视角。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.