Desenvolvimento da pré-eclâmpsia e o gene STOX1: uma revisão sistemática e metanálise

Abstract

Preeclampsia (PE) is a multifactorial hypertensive disorder of pregnancy and a major cause of maternal and perinatal morbidity and mortality worldwide. Polymorphisms in the STOX1 gene (Y153H and -922 T>C) have been associated with susceptibility to PE, but findings remain inconsistent. Thus, the objective of this study was to assess the association between STOX1 gene polymorphisms and the development of PE through a systematic review and meta-analysis. This review followed the PRISMA guidelines and was registered in PROSPERO (CRD42023465306). A search was conducted in eight databases to identify studies investigating STOX1 gene polymorphisms in pregnant women with PE versus normotensive controls. Observational studies with no restrictions on date or language were included, provided they involved women with PE and STOX1 polymorphisms. Two reviewers independently selected and extracted the data, and a third reviewer was consulted in cases of discrepancies or conflicts. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed or random-effects models, depending on heterogeneity assessed by the I² statistic. A total of 300 studies were retrieved from the databases, and after the selection process, four were included, comprising 1,906 cases and 3,019 controls. Three studies investigated the Y153H variant and found no significant association with PE. The meta-analyses showed high heterogeneity, especially in the allele comparison (I² = 99.6%). Only one study assessed the -922 T>C polymorphism and found a significant association with PE, particularly early-onset PE (OR = 2.01; 95% CI [1.11–3.65]; p = 0.02); however, it was not included in the meta-analysis due to the lack of comparable studies. The included studies had good methodological quality, scoring 7 stars on the NOS. No consistent evidence was found that the STOX1 Y153H polymorphism is associated with PE. Although some studies suggest an association with PE, a comparative consistency analysis could not be performed. Larger, multiethnic studies including clinical, genetic, and transcriptomic data are needed to elucidate the role of STOX1 in the pathogenesis of PE.