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
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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.
子痫前期与心血管疾病进展相关的基因组变异:一项系统综述
背景:有先兆子痫(PE)病史的女性患晚年心血管疾病(CVD)的风险高达5倍。虽然已知PE和CVD具有共同的临床和分子特征,但随着时间的推移,研究它们共同的基因组学(遗传学、表观遗传学或转录组学)变异的研究有限。因此,我们试图系统地回顾文献,以确定专注于PE后CVD基因组进展的纵向研究。方法通过OVID检索PubMed、Scopus、Web of Science、Embase等原始文献。1980年1月1日至2023年7月28日期间发表的研究PE和CVD基因组学的研究符合入选条件。纳入的研究是根据Cochrane系统评价指南和PRISMA 2020清单进行筛选的。使用纽卡斯尔-渥太华量表进一步评估符合条件的文章的质量。结果共筛选9231篇文献,其中14篇进行了质量评价。经过进一步评价,6项研究被纳入最后审查。所有这六项研究在CVD/危险因素作为结果、基因定位方法和不同的靶基因方面都是异质的。相关基因为RGS2、LPA和AQP3,以及microrna miR-122-5p、miR-126-3p、miR-146a-5p和miR-206。此外,鉴定出12个差异甲基化区域可能与PE后的晚年CVD相关。所有六项研究中唯一的共同变量是病例对照研究设计的使用。我们的研究结果为研究PE后CVD的基因组研究的异质性提供了重要的见解,并强调了纵向研究的迫切需要,以进一步研究PE后CVD进展的遗传变异。
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