Genomic variation associated with cardiovascular disease progression following preeclampsia: a systematic review

Gayathry Krishnamurthy; Phuong Tram Nguyen; Bao Ngoc Tran; Hoang T Phan; Shaun P Brennecke; Eric K Moses; Phillip E Melton

doi:10.3389/fepid.2023.1221222

Genomic variation associated with cardiovascular disease progression following preeclampsia: a systematic review

Front Epidemiol. 2023 Oct 16:3:1221222. doi: 10.3389/fepid.2023.1221222. eCollection 2023.

Authors

Gayathry Krishnamurthy¹, Phuong Tram Nguyen¹, Bao Ngoc Tran², Hoang T Phan¹, Shaun P Brennecke^{3

4}, Eric K Moses¹, Phillip E Melton^{1

5}

Affiliations

¹ Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, Australia.
² Wicking Dementia Research and Education Center, College of Health and Medicine, The University of Tasmania, Hobart, TAS, Australia.
³ Pregnancy Research Centre, Department of Maternal-Fetal Medicine, The Royal Women's Hospital, Melbourne, VIC, Australia.
⁴ Department of Obstetrics and Gynaecology, The Royal Women's Hospital, The University of Melbourne, Melbourne, VIC, Australia.
⁵ School of Global and Population Health, The University of Western Australia, Crawley, WA, Australia.

Abstract

Background: Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE.

Methods: A literature search of primary sources through PubMed, Scopus, Web of Science and Embase via OVID was performed. Studies published from January 1, 1980, to July 28, 2023, that investigated genomics in PE and CVD were eligible for inclusion. Included studies were screened based on Cochrane systematic review guidelines in conjunction with the PRISMA 2020 checklist. Eligible articles were further assessed for quality using the Newcastle-Ottawa scale.

Results: A total of 9,231 articles were screened, with 14 studies subjected to quality assessment. Following further evaluation, six studies were included for the final review. All six of these studies were heterogeneous in regard to CVD/risk factor as outcome, gene mapping approach, and in different targeted genes. The associated genes were RGS2, LPA, and AQP3, alongside microRNAs miR-122-5p, miR-126-3p, miR-146a-5p, and miR-206. Additionally, 12 differentially methylated regions potentially linked to later-life CVD following PE were identified. The only common variable across all six studies was the use of a case-control study design.

Conclusions: Our results provide critical insight into the heterogeneous nature of genomic studies investigating CVD following PE and highlight the urgent need for longitudinal studies to further investigate the genetic variation underlying the progression to CVD following PE.

Keywords: cardiovascular disease; epigenetic; genetic; genomic; preeclampsia; pregnancy hypertensive disorder; transcriptomic.

Publication types

Review

Grants and funding

All the funds required for this systematic review were covered by National Health and Medical Research Council (NHMRC), Australia, research grant (APP2001203) and Tasmania Graduate Research Scholarship (TGRS) from the University of Tasmania, Hobart, Australia.