Preeclampsia Genomic Susceptibility Factors in Populations of African Ancestry: A Systematic Review and Meta-Analysis

Abstract

The aim of this review is to examine the contribution of genomic variation to preeclampsia susceptibility in Africans. PubMed/Medline, Scopus, African Index Medicus and Sabinet African Journals databases were used to access studies conducted in populations of African descent focussing on the genomics of preeclampsia. Studies were selected according to PRISMA guidelines and assessed for quality and risk of bias using the Critical Appraisal Skills Programme (CASP) and Joanna Briggs Institute (JBI) checklists. Meta-analysis was conducted using a random effects model, and publication bias was evaluated using the Eggers test and funnel plots. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to evaluate the certainty of evidence outcomes. Sixty-six (66) studies reporting on genomics of preeclampsia were retrieved. Forty-four (44) studies had a quality assessment score ≥75%. Vascular pathway genes (<i>GNB3</i>, <i>FLT1</i>, <i>NOS3</i> and <i>VEGFC</i>; OR (95% CI): 1.61 (1.38-1.88); <i>I</i>²: 0.0%, <i>p</i> = 0.87; GRADE: low certainty), immune/inflammatory pathway genes (<i>APOL1</i>, <i>ERAP2</i>, <i>HLA-G</i>, <i>IL-1β</i>, <i>LEPR</i> and <i>TNF-α</i>; OR (95% CI): 2.07 (1.68-2.54); <i>I</i>²: 42.2%, <i>p</i> = 0.04; GRADE: low certainty) and cellular homeostasis genes (<i>GLUT9</i>, <i>URAT1</i>, <i>SLC4A1</i> and <i>SLCO4C1</i>; OR (95% CI): 1.65 (1.43-1.91); <i>I</i>²: 0.0%, <i>p</i> = 0.99; GRADE: low certainty) showed pooled effect estimates suggestive of moderate to increased preeclampsia risk. <i>APOL1</i> G1 or G2 risk alleles seemed to contribute 1.70-fold (95% CI: 1.39-2.07; <i>I</i>²: 0.0%; <i>p</i> = 0.51; GRADE: low certainty), respectively, to overall preeclampsia risk. Vascular, immune/inflammatory and cellular homeostasis genes may be ideal starting points for future research, and further validation of the role of <i>APOL1</i> G1 or G2 risk alleles in preeclampsia may be essential.