TY - JOUR
T1 - Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B–VEGF-DNMT1 Axis
AU - Setiawan, Arief
AU - Anwar, Ruswana
AU - Syamsunarno, Mas Rizky Anggun Adipurna
AU - Mose, Johanes Cornelius
AU - Santoso, Budi
AU - Maskoen, Ani Melani
AU - Permadi, Wiryawan
AU - Setiabudiawan, Budi
AU - Dhamayanti, Meita
AU - Hidayat, Yudi Mulyana
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/6
Y1 - 2023/6
N2 - Background: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. Methods: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. Results: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = −0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24–33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57–3.49, p = 0.113), although the relationship was not statistically significant. Conclusion: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.
AB - Background: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. Methods: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. Results: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = −0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24–33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57–3.49, p = 0.113), although the relationship was not statistically significant. Conclusion: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.
KW - DNA methyltransferase
KW - VEGF
KW - endometriosis
KW - epigenetic
KW - low birth weight
KW - progesterone receptor B
UR - http://www.scopus.com/inward/record.url?scp=85163997441&partnerID=8YFLogxK
U2 - 10.3390/diagnostics13122085
DO - 10.3390/diagnostics13122085
M3 - Article
AN - SCOPUS:85163997441
SN - 2075-4418
VL - 13
JO - Diagnostics
JF - Diagnostics
IS - 12
M1 - 2085
ER -