Associations of HSD17B1 Gene Expression with its DNA Methylation and Estradiol Level in Polycystic Ovary Syndrome Indonesian Patients

Puspita, Rina and Hestiantoro, Andon and Agustina, Rina and Handayani, Nining and Sirait, Batara I. and Polim, Arie Adrianus and Asmarinah, Asmarinah (2024) Associations of HSD17B1 Gene Expression with its DNA Methylation and Estradiol Level in Polycystic Ovary Syndrome Indonesian Patients. OnLine Journal of Biological Sciences, 24 (2). pp. 154-169. ISSN 2410-8561

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Abstract

PCOS's origin and mechanism are still unknown. Epigenetics has been linked to PCOS in an increasing number of studies in recent years. The most extensively researched epigenetic alteration is DNA methylation. During organismal development, DNA methylation can control gene expression by altering transcription factor binding. The alterations in DNA methylation are directly associated with follicular development in PCOS. Studies show that increased levels of pregnenolone and estrogen in the follicular fluid may affect follicle formation in PCOS patients; the process is largely associated with the expression of HSD17B1. There is evidence to suggest that these levels may have an impact on follicle development in PCOS patients. The mechanism for this effect is partially linked to HSD17B1 expression, which catalyzes the final step in estrogen biosynthesis, 17β- estradiol (E2). We speculated that defects in DNA methylation increase gene dysregulation, resulting in decreased mRNA expression of HSD17B1, which eventually generates insufficient E2 in PCOS patients. The objective of this study is to investigate DNA methylation, mRNA expression, and E2 level in PCOS patients and healthy women groups; the correlation between DNA methylation and mRNA expression in PCOS patients; and the correlation between mRNA expression and E2 serum level in PCOS patients. We provided informed consent to participants; we studied 60 female patients, 30 PCOS patients and 30 healthy women served as the control group, we used the Methyl-Specific PCR (MSP) method and quantitative PCR (qPCR) for DNA methylation and mRNA expression analyses, respectively; and we examined E2 serum levels and hormonal levels. The methylation of the HSD17B1 gene in PCOS women was 42.64% and a healthy group showed 53.80% (p = 0.160). The two groups' differences were not statistically significant. The relative expression value of the HSD17B1 gene was 0.70- fold lower compared with the healthy women (p = 0.003) group. Significant variances were between the two groups. The average E2 serum level in the PCOS group is 25.78 pg/mL and in the healthy women group, it is 36.74 pg/mL. Compared to the group of healthy women, the PCOS group had a decreased E2 serum level. The correlation of DNA methylation level versus mRNA expression in PCOS patients is not significant. (p = 0.076). A significant negative association has been seen between the mRNA. There is a significant negative correlation between the mRNA expression of the HSD17B1 gene and serum E2 levels. (p = 0.020). "The more down-regulated mRNA expression of the HSD17B1 gene, the lower serum E2 levels." The integrated analysis in this study was hypomethylated DNA and down-regulated mRNA expression of HSD17B1 genes. The hypomethylated DNA was not involved in down-regulating mRNA expression. Therefore, down-regulated mRNA expression of the HSD17B1 gene in PCOS patients can cause lower E2 levels in PCOS, preventing cell growth and potentially contributing to the cause of PCOS pathogenesis. Keywords: HSD17B1 Gene, DNA Methylation, mRNA Expression, Estradiol, Polycystic Ovary Syndrome

Item Type: Article
Subjects: MEDICINE
Depositing User: Mr Sahat Maruli Tua Sinaga
Date Deposited: 14 Mar 2024 09:18
Last Modified: 27 Mar 2024 09:22
URI: http://repository.uki.ac.id/id/eprint/14057

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