Genetic risk factors in preeclampsia: A meta-analysis of VEGF (rs699947), and LEPR (rs1137100, rs1137101) polymorphisms

Background and aim: Early identification of biomarkers for preeclampsia (PE) is crucial, as the condition can lead to significant maternal and fetal morbidity and mortality. Genetic screening based on the pathophysiology of PE, particularly involving polymorphisms such as VEGF-A (rs699947), LEPR (rs1137100), and LEPR (rs1137101), shows promise for early risk assessment. This study aimed to evaluate the association of these polymorphisms with PE. Methods: A systematic search was conducted in MEDLINE, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Springer, and ProQuest. The genetic associations were evaluated using genotype-based and allelic comparison models. The methodological quality of the included studies was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Statistical analyses were performed using Review Manager software (version 5.4). Results: In the VEGF-A (rs699947) analysis across eight studies, the CA genotype was associated with a reduced risk of preeclampsia compared with the CC genotype (OR = 0.47, 95% CI: 0.29–0.78; p < 0.005). The CA genotype was also associated with a higher risk compared with AA (OR: 4.08, 95% CI: 2.77–6.01; p < 0.001). For the LEPR (rs1137100) polymorphism, AG vs. GG showed a significant association, with the AG genotype having a higher risk of preeclampsia (OR: 10.78, 95% CI: 1.38–84.00; p < 0.05). Conclusions: For VEGF-A (rs699947), the CC genotype showed the highest risk, followed by CA, while AA was associated with the lowest risk, and for LEPR (rs1137100), the AG genotype was associated with an increased risk of preeclampsia.