Plasminogen Activator Inhibitor-1 Gene Polymorphisms in Pre-Eclampsia

D'Elia, Angela; Fabbro, Dora; Driul, Lorenza; Barillari, Giovanni; Marchesoni, D.; Damante, Giuseppe

doi:10.1055/s-0030-1270334

Cited by 10 publications

(11 citation statements)

References 80 publications

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“…The 4G PAI-1 polymorphism has been the most commonly studied fibrinolytic variant in relation to obstetric complications and venous thromboembolism; however, over 100 other polymorphisms in the PAI-1 gene have been described, although many of these are unlikely to contribute to a functional defect [19]. Many of these polymorphisms are also co-inherited in haplotype blocks due to linkage disequilibrium [10,19]. Furthermore, other fibrinolytic pathway polymorphisms, including polymorphisms in the thrombin activatable fibrinolysis inhibitor (TAFI) gene, have been described in association with impaired fibrinolysis and an increased risk of venous thromboembolism [20], raising the possibility that it is not a single polymorphism responsible for the phenotypic effects of adverse pregnancy outcomes, but rather the integrity of the entire fibrinolytic and indeed hemostatic pathway as a whole.…”

Section: Discussionmentioning

confidence: 99%

“…The possible association between this polymorphism and adverse pregnancy outcomes has been reported but the results are conflicting [9][10][11]. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Said

Tsui

Borg

et al. 2012

Journal of Thrombosis and Haemostasis

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Said

Tsui

Borg

et al. 2012

Journal of Thrombosis and Haemostasis

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“…In the worst cases, these are the very frightening DIC (1047, 1069–1073) that can, of course, also emerge as a consequence of sepsis (1074–1080). Variations in the plasminogen activator inhibitor-1 may contribute to the hypofibrinolysis observed (1081–1083). …”

Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…This physiological mechanism, involving both coagulation cascade and fibrinolysis, is pathologically exacerbated during PE [189,190]. Accordingly, deregulation of the coagulation cascade and hypofibrinolysis appear to play a central role in the development of PE [191,192].…”

Section: Genes Involved In Thrombophilia and Hypofibrinolysismentioning

confidence: 99%

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

Danese¹,

Montagnana²,

Fava³

2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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Primary hypertension is a very common disorder particularly in the aging population but hypertensive disorders can appear earlier in life, especially when obesity and unhealthy lifestyle are present. Also pregnant women can be at risk of developing gestational hypertension and/or pre-eclampsia, which causes complications in nearly 7% of pregnancies. These "special" populations could be regarded as natural models suited to reveal mechanisms of hypertension development which are either common to other forms of hypertension, including primary hypertension or specific to these populations. Recent studies in the field of genetics of primary hypertension have used new powerful tools, such as genome-wide association studies (GWAS) and sequencing, but studies about hypertension during childhood and in pregnancy have seldom used high-throughput technologies and the knowledge in this field comes mostly from the candidate gene approach. In this review we summarize some interesting results from genetic studies conducted in childhood and adolescence and during pregnancy and underline the need to apply modern technologies in these potentially very fruitful populations.

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Plasminogen Activator Inhibitor-1 Gene Polymorphisms in Pre-Eclampsia

Cited by 10 publications

References 80 publications

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

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

A Dormant Microbial Component in the Development of Preeclampsia

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

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