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Hypomethylation of the Promoter Region of the Vascular Endothelial Growth Factor (VEGF) Gene and It’s Low Expression in Placenta as a Risk Factor for Preeclampsia Bay, Godefridus Paulo; Kusuma, A.A.N Jaya; Darmayasa, I Made; Mahendra, I Nyoman Bayu; Mahayasa, Putu Doster; Marta, Kadek Fajar
Indonesian Journal of Obstetrics & Gynecology Science Volume 8 Nomor 3 November 2025
Publisher : Dep/SMF Obstetri & Ginekologi Fakultas Kedokteran Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/obgynia.v8i3.923

Abstract

Objective: This study aimed to determine the association between hypomethylation of VEGF gene promoter region and low VEGF expression in the placenta as a potential risk factor for preeclampsia.Methods: An observational case-control study was conducted involving pregnant women with preeclampsia and normotensive controls. Placental tissue samples were collected and analysed for DNA methylation status of the VEGF gene promoter using quantitative real-time PCR. VEGF expression levels in placental tissue were measured using ELISA. Results: Significant hypomethylation of the VEGF promoter region was observed in placenta samples from preeclamptic women compared to controls. This finding correlated with decreased VEGF expression. These results indicate that reduced VEGF expression due to promoter hypomethylation may impair placental vascularization, contributing to preeclampsia.Conclusions: Hypomethylation of the VEGF promoter and subsequent reduction in placental VEGF expression may serve as early biomarkers to predict preeclampsia. These results highlight the importance of epigenetic regulation in preeclampsia pathogenesis and suggest potential targets for early diagnosis and intervention.Hipometilasi Regio Promoter Gen Vascular Endothelial Growth Factor (VEGF) dan Ekspresi Vascular Endothelial Growth Factor (VEGF) yang Rendah pada Plasenta sebagai Faktor Risiko PreeklampsiaAbstrakTujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara hipometilasi pada daerah promoter gen VEGF dan rendahnya ekspresi VEGF di plasenta sebagai faktor risiko potensial terjadinya preeklampsia.Metode: Penelitian observasional dengan desain kasus-kontrol ini melibatkan ibu hamil dengan preeklampsia dan kontrol normotensif. Sampel jaringan plasenta dikumpulkan dan dianalisis untuk menentukan status metilasi DNA pada daerah promoter gen VEGF menggunakan quantitative real-time PCR. Tingkat ekspresi VEGF dalam jaringan plasenta diukur menggunakan metode ELISA.Hasil: Didapatkan hipometilasi yang signifikan pada daerah promoter gen VEGF pada jaringan plasenta ibu dengan preeklampsia dibandingkan kelompok kontrol. Temuan ini berkorelasi dengan penurunan ekspresi VEGF. Hasil tersebut menunjukkan bahwa penurunan ekspresi VEGF akibat hipometilasi promoter dapat mengganggu vaskularisasi plasenta, sehingga berperan dalam patogenesis preeklampsia.Kesimpulan: Hipometilasi pada daerah promoter gen VEGF dan penurunan ekspresi VEGF di plasenta dapat berfungsi sebagai biomarker awal untuk memprediksi terjadinya preeklampsia. Hasil ini menyoroti pentingnya regulasi epigenetik dalam patogenesis preeklampsia serta membuka peluang untuk diagnosis dini dan intervensi yang lebih tepat.Kata kunci: Preeklampsia, VEGF, Hipometilasi, Plasenta, Epigenetik
Promoter Methylation and Low Placental Expression of Metalloproteinase (MMP)-9, Human Leukocyte Antigen (HLA)-G, Vascular Endothelial Growth Factor (VEGF), and Highly Soluble Endoglin (sEng) as Risk Factors for Preeclampsia Kusuma, Anak Agung Ngurah Jaya; Darmayasa, I Made; Mulyantari, Ni Kadek; Mayasari, Ni Nyoman Wistya Tri; Sutandi, Chatrine; Bay, Godefridus Paulo; Nugraha, Cokorda Gde Angga Ary
The Indonesian Biomedical Journal Vol 18, No 1 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i1.3921

Abstract

BACKGROUND: Dysregulated expressions of metalloproteinase (MMP)-9, human leucocyte antigen (HLA)-G, vascular endothelial growth factor (VEGF), and soluble endoglin (sEng) reflect impaired angiogenesis, immune tolerance, endothelial function, and trophoblast invasion that characterize abnormal placental development in preeclamptic (PE) pregnancies. However, the role of promoter methylation of these markers in linking the pathways to altered protein expression remains unclear. Hence, this study compared promoter methylation and placental expression of MMP-9, HLA-G, VEGF, and sEng between women with PE and normotensive pregnancies, and evaluate their diagnostic performance as potential biomarkers.METHODS: This case–control study included 30 women with PE and 30 controls. Placental tissue samples were collected within 15 minutes postpartum. Placental promoter methylation was assessed using methylation-specific polymerase chain reaction (PCR), and protein expression was measured using enzyme-linked immunosorbent assay (ELISA). Group differences were analyzed, diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves, and associations were expressed as adjusted odds ratios (AOR).RESULTS: Compared with controls, placentas from women with PE significantly showed higher methylation of HLA-G (58.9% vs. 37.3%) and sEng (6.7% vs. 4.1%), and lower methylation of VEGF (30.4% vs. 48.1%) and MMP-9 (36.1% vs. 44.9%). Expression of MMP-9, HLA-G, and VEGF was significantly reduced, while sEng expression was increased in PE. Multivariate analysis identified HLA-G hypermethylation (AOR 5.36), VEGF hypomethylation (AOR 8.55), sEng methylation (AOR 4.57), low expression of MMP-9, HLA-G, and VEGF, and high sEng expression (AOR 4.77) as independent predictors of PE. sEng expression demonstrated the best discrimination (AUC 0.835), followed by sEng methylation (AUC 0.785) and HLA-G methylation (AUC 0.774).CONCLUSION: PE is associated with distinct placental methylation–expression alterations, with sEng- and HLA-G–related markers showing the strongest diagnostic value.KEYWORDS: preeclampsia, DNA methylation, angiogenesis, MMP-9, HLA-G, sEng, placenta, epigenetics