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All Journal Medicina E-Jurnal Medika Udayana The Indonesian Biomedical Journal Indonesian Journal of Obstetrics & Gynecology Science ISM (Intisari Sains Medis) : Jurnal Kedokteran Indonesian Journal of Perinatology Journal Research of Social Science, Economics, and Management
Evert Solomon Pangkahila
Department Of Obstetrics And Gynecology, Division Of Maternal-Fetal Medicine,Udayana University Hospital-Bali
Biochemistry, Genetics & Molecular Biology Environmental Science Health Professions Medicine & Pharmacology Nursing Public Health

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Hypomethylation of the Soluble Fms-like Tyrosine Kinase 1 (sFlt-1) Gene Promoter Region and Elevated sFlt-1 Placental Expression as Risk Factors for Preeclampsia Kusuma, Anak Agung Ngurah Jaya; Darmayasa, I Made; Putra, I Gede Mega; Suardika, Anom; Pangkahila, Evert Solomon; Duarsa, Vidya Saraswati Putri; William, William
The Indonesian Biomedical Journal Vol 17, No 4 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i4.3744

Abstract

BACKGROUND: Preeclampsia significantly contributes to maternal and fetal morbidity and mortality worldwide, marked by an imbalance of angiogenic factors, particularly increased soluble Fms-like tyrosine kinase-1 (sFlt-1), leading to endothelial dysfunction. Epigenetic regulation, including DNA methylation of the sFlt-1 promoter, has been suggested to influence sFlt-1 expression, but the data in Indonesian population are limited. This study was perfmed to determine whether hypomethylation of the sFlt-1 promoter and elevated placental sFlt-1 expression are associated with increased risk of preeclampsia.METHODS: A case-control study was conducted involving 30 women with preeclampsia and 30 normotensive pregnant women. Subjects were selected based on eligibility criteria that included singleton pregnancy and gestational age of ≥37 weeks. DNA methylation of the sFlt-1 promoter was assessed using methylation-specific polymerase chain reaction (PCR), and sFlt-1 expression was measured by enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Mann-Whitney U, Chi-square tests, Receiver-operating characteristic (ROC) curve analysis, and multivariate logistic regression, were performed to evaluate the relationship between methylation levels, gene expression, and preeclampsia risk.RESULTS: The preeclampsia group had significantly lower methylation levels of sFlt-1 promoter and higher placental sFlt-1 expression (both p<0.001). Hypomethylation of sFlt-1 promoter (adjusted odd ratio (AOR): 21.18; 95% CI: 2.49–179.72; p=0.005), high sFlt-1 expression (AOR: 12.55; 95% CI: 1.95–80.83; p=0.008), and obesity (AOR: 11.15; 95% CI: 2.01–61.78; p=0.006) were identified as independent risk factors for preeclampsia.CONCLUSION: Hypomethylation of sFlt-1 promoter and elevated placental sFlt-1 expression are significant independent risk factors for preeclampsia. These findings suggest that hypomethylation of sFlt-1 promoter and elevated placental sFlt-1 expression may serve as potential epigenetic biomarkers for early detection and targeted intervention in preeclampsia.KEYWORDS: preeclampsia, sFlt-1, gene expression, hypomethylation, placenta, risk factor
Co-Authors Adhi Pribadi Agrifa Eko Albert Sembiring Ahmad, Nurmi Aldiansyah, Dudy Aldika Akbar, Muhammad Ilham Aloysius Suryawan Andonotopo, Wiku Anom Suardika Bachnas, Muhammad Adrianes Bambang Rahardjo Cut Meurah Yeni Daniel H. Susanto Denni Prasetyo Duarsa, Vidya Saraswati Putri Endang Sri Widiyanti Hartanto Hartanto I Gede Mega Putra I Ketut Surya Negara I Ketut Suwiyoga I Made Darmayasa I Nyoman Gede Budiana I Nyoman Hariyasa Sanjaya Ida Bagus Putra Adnyana Julian Dewantiningrum Kurjak, Asim Kusuma, Anak Agung Ngurah Jaya Manuaba, Ida Bagus Gede Fajar Ni Kadek Mulyantari Nuswil Bernolian Pramono, Mochammad Besari Adi Putu Doster Mahayasa Rey Jauwerissa Ryan S. Mulyana Ryan Saktika Mulyana Satriawan, Nyoman Gede Dikawijaya Sri Sulistyowati Stanojevic, Milan Surya, I Gede Ngurah Harry Wijaya Theresia Monica Rahardjo Tjokorda Gde Agung Suwardewa William Alexander Setiawan Wiradnyana, Anak Agung Gede Putra