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Investigating Molecular Biomarkers During Gestational Diabetes Mellitus
Thesis (PhD)--University of Pretoria, 2019.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2020
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| _version_ | 1867613522817449984 |
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| access_status_str | Open Access |
| author2 | Pheiffer, Carmen |
| author_browse | Pheiffer, Carmen |
| author_facet | Pheiffer, Carmen |
| collection | Thesis |
| dc_rights_str_mv | © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD)--University of Pretoria, 2019. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/73566 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:29.594Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/73566 Investigating Molecular Biomarkers During Gestational Diabetes Mellitus Pheiffer, Carmen Stephanie.Dias@mrc.ac.za Adam, Sumaiya Rheeder, Paul Dias, Stephanie Charmaine UCTD Reproductive Biology Gestational Diabetes Mellitus Molecular Biomarkers Epigenetics Genetics SDG-03: Good health and well-being SDG-17: Partnerships for the goals Thesis (PhD)--University of Pretoria, 2019. Introduction: Gestational diabetes mellitus (GDM) is a significant public health concern, due to its association with short- and long-term complications in both mothers and offspring. DNA methylation and single nucleotide polymorphisms (SNPs) offer potential to serve as molecular biomarkers, which may lead to improved detection of GDM with positive effects on health outcomes. Aim: The aim of this study was to investigate whether DNA methylation and SNPs are associated with GDM and may offer potential as molecular biomarkers for GDM in South Africa (SA). Methods: This study followed a two-pronged approach. Firstly, literature searches were conducted to collate and synthesise all published articles reporting on the prevalence of GDM in SA, the screening and diagnostic strategies used, and the current status of DNA methylation and SNPs as biomarkers for GDM. Secondly, we conducted experiments to investigate global (n=201), genome-wide (n=24) and gene-specific DNA methylation (n=286) of the adiponectin gene (ADIPOQ) in whole blood of women with and without GDM, using an Enzyme-Linked Immunosorbent Assay, a methylationEPIC BeadChip Array and pyrosequencing, respectively. In addition, genotype and allele frequencies of ADIPOQ rs266729 and rs17300539, and methylenetetrahydrofolate reductase (MTHFR) rs1801133 were determined, using quantitative real-time PCR (n=449) and DNA sequencing for validation. Results: The literature search showed that the prevalence of GDM in SA has increased over the years. Furthermore, it showed that the lack of uniformity in screening and diagnosis between and within countries hamper the accurate detection of GDM. Lastly, the literature search identified several studies that support the use of DNA methylation and SNPs as potential biomarkers for GDM. Experimentally, we showed no differences in global DNA methylation between GDM and non-GDM groups. Interestingly, global DNA methylation levels were 18% (p=0.012) higher in obese compared to non-obese pregnant women. Genome-wide methylation analysis identified 1046 differentially methylated CpG sites (associated with 939 genes) (Cut-off threshold: M>0.06 and p<0.01). Among the top five CpG sites identified, one CpG mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which has been shown to regulate insulin production and secretion. Two CpG sites (-3410: p=0.048 and -3400: p=0.004) in the ADIPOQ promoter were hypomethylated during GDM in HIV negative, but not in HIV positive women. Lastly, no association between the ADIPOQ and MTHFR polymorphisms and GDM was observed in our population. Conclusion: To our knowledge, this is the first study to investigate the association between DNA methylation or ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms and GDM in SA. Findings suggest that gene-specific, but not global methylation nor SNPs rs266729, rs17300539 and rs1801133, may offer potential as molecular biomarkers of GDM in this population. Future longitudinal studies in larger samples that include both HIV negative and positive pregnant women are warranted to explore the candidacy of DNA methylation as molecular biomarkers for GDM. National Research Foundation (NRF) of South Africa, Thuthuka Grant (unique grant no. 99391). South African Medical Research Council (SAMRC) em2026 Obstetrics and Gynaecology PhD Unrestricted SDG-03: Good health and well-being SDG-17: Partnerships for the goals 2020-02-26T11:26:57Z 2020-02-26T11:26:57Z 2020-04-24 2019 Thesis Dias, SC 2019, Investigating Molecular Biomarkers During Gestational Diabetes Mellitus, PhD Thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/73566> A2020 http://hdl.handle.net/2263/73566 en © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Reproductive Biology Gestational Diabetes Mellitus Molecular Biomarkers Epigenetics Genetics SDG-03: Good health and well-being SDG-17: Partnerships for the goals Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title | Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title_full | Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title_fullStr | Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title_full_unstemmed | Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title_short | Investigating Molecular Biomarkers During Gestational Diabetes Mellitus |
| title_sort | investigating molecular biomarkers during gestational diabetes mellitus |
| topic | UCTD Reproductive Biology Gestational Diabetes Mellitus Molecular Biomarkers Epigenetics Genetics SDG-03: Good health and well-being SDG-17: Partnerships for the goals |
| url | http://hdl.handle.net/2263/73566 |