Pediatr Res. 2026 May 12. doi: 10.1038/s41390-026-05015-2. Online ahead of print.
ABSTRACT
BACKGROUND: Patent ductus arteriosus (PDA) is a common congenital heart disease. While the ACTC1 gene is crucial for heart development, the role of its promoter variants in PDA pathogenesis remains unclear.
METHODS: Peripheral blood DNA from 745 subjects (427 PDA patients and 318 healthy controls) was sequenced. Functional assessments included transcriptional activity assays in mouse cardiomyocytes, electrophoretic mobility shift assays (EMSA), and JASPAR database analysis.
RESULTS: Eight variants in the ACTC1 promoter region were identified. Four of these, including a novel heterozygous variant, were found exclusively in PDA patients. These variants significantly altered ACTC1 promoter transcriptional activity (p<0.05). Furthermore, EMSA and JASPAR analyses indicated that these variants affect ACTC1 transcription by destroying or generating transcription factor binding sites.
CONCLUSION: This study provides the first evidence associating ACTC1 promoter variants with PDA occurrence, offering novel perspectives on the pathogenesis and potential therapeutic strategies for PDA.
IMPACT: DNA from 745 human subjects was sequenced for ACTC1 gene promoter region variants with four variants found only in PDA patients and one was novel. EMSA and dual luciferase reporter experiments found these variants reduced transcriptional activity. Prediction by JASPAR database indicated that these variants alter the transcription factor binding sites. The study, for the first time, confirmed that there are variants at the ACTC1 gene promoter region and these variants cause cellular dysfunction. The variants found in this study suggest the possible pathological role in the formation of PDA.
PMID:42120536 | DOI:10.1038/s41390-026-05015-2