The PAI‐1 4G/5G polymorphism is not associated with an increased risk of adverse pregnancy outcome in asymptomatic nulliparous women

Abstract

Summary. Background: Plasminogen activator inhibitor type 1 (PAI‐1) is an important regulator of fibrinolysis. A common deletion polymorphism that results in a sequence of 4G instead of 5G in the promoter region of the gene is associated with a small increase in the risk of venous thromboembolism. Its potential association with adverse pregnancy events remains controversial. Objective: We aimed to assess the impact of the 4G PAI‐1 polymorphism on pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism. Patients/methods: This study represents a secondary investigation of a prior prospective cohort study investigating the association between inherited thrombophilias and adverse pregnancy events in Australian women. Healthy nulliparous women were recruited to this study prior to 22 weeks gestation. Genotyping for the 4G/5G PAI‐1 gene was performed using Taqman assays in an ABI prism 7700 Sequencer several years after the pregnancy was completed. Pregnancy outcome data were extracted from the medical record. The primary outcome was a composite comprising development of severe pre‐eclampsia, fetal growth restriction, major placental abruption, stillbirth or neonatal death. Results: Pregnancy outcome data were available in 1733 women who were successfully genotyped for this polymorphism. The primary composite outcome was experienced by 139 women (8% of the cohort). Four hundred and fifty‐nine women (26.5%) were homozygous for the 4G deletion polymorphism, while 890 (51.4%) were heterozygous. Neither homozygosity nor heterozygosity for the PAI‐1 4G polymorphism was associated with the primary composite outcome (homozygous OR = 1.30, 95% CI = 0.81–2.09, P = 0.28, heterozygous OR = 0.84, 95% CI = 0.53–1.31, P = 0.44) or with the individual pregnancy complications. Conclusion: The PAI‐1 4G polymorphism is not associated with an increase in the risk of serious adverse pregnancy events in asymptomatic nulliparous women.

Association of Plasminogen Activator Inhibitor-Type 1 (-675 4G/5G) Polymorphism with Pre-Eclampsia: Systematic Review

“…Following screening, we selected 24 articles for full text assessment [22]–[45]. 12 studies met all inclusion criteria and were included in the meta-analysis [22]–[33].…”

“…We included 12 studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls with uncomplicated pregnancies participated [22]–[33]. Most studies were small (number of cases range from 24 to 403).…”

“…Eleven of the studies used a case-control design [22]–[32]. One was a cohort study [33]. Other study characteristics are described in table 1.…”

“…All participants fulfilled internationally-recognised criteria for pre-eclampsia (sustained blood pressure ≥140/90 mm Hg with proteinuria ≥300 mg/24 h, after 20 weeks' gestation). In six studies, participation was restricted to women with severe pre-eclampsia (sustained blood pressure ≥160/110 mm Hg), eclampsia or HELLP syndrome [24], [27], [29], [31]–[33].…”

“…One study in South Africa enrolled only Black, Zulu language-speaking women [24]. One study recruited Caucasian women in Australia [33]. In a Brazilian study, most participants were Caucasian but the ethnicity of 29% of participants was not described [30].…”