ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

Krogh, Anne-Sophie von; Hovinga, Johanna A. Kremer; Romundstad, Pål Richard; Roten, Linda Tømmerdal; Lämmle, Bernhard; Waage, Anders; Quist‐Paulsen, Petter

doi:10.1016/j.thromres.2015.06.022

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…In accordance with our findings, several studies found statistically significant decreases in ADAMTS13 activity in preeclamptic women's serums over healthy controls [6,11,[13][14][15][16][17]. A few articles, however, found no significant differences between the two groups of individuals, suggesting that ADAMTS13 activity is not associated with PE [18][19][20]. Consequently, besides the strong correlation between significantly low levels of ADAMTS13 activity (below 10-20%) and TTP, a more average level cannot rule out preeclampsia.…”

Section: Discussionsupporting

confidence: 89%

“…In our study, risk-factor variants were found in ADAMTD13, C3, and Complement Factor H (CFH) genes. It is worth noting that the study conducted by von Krogh et al did not find any correlation between the three investigated gene variants of ADAMTS13 and PE, including the rs28647808 variant, which our own study characterized as deleterious [20].…”

Section: Discussioncontrasting

confidence: 43%

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Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study

Venou,

Vetsiou,

Varelas

et al. 2024

JPM

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Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.

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Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 43%

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study

Venou,

Vetsiou,

Varelas

et al. 2024

JPM

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“…In contrast, only a few papers reported no differences between the two groups, suggesting that ADAMTS13 activity is not significantly associated with PE [ 19 , 20 , 21 ]. In the study of Yoshida et al, pregnant women with HELLP syndrome were also included in the sample, but the sizes of the patient group ( n = 13) and the control group ( n = 128) are obviously inequivalent [ 20 ] Interestingly, according to von Krogh et al, no statistically significant differences were detected concerning lower levels, genotype, allele, and haplotype of the ADAMTS13 variants between the preeclamptic and the healthy control group of pregnant women [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…The question is whether ADAMTS13 could be considered a reliable biomarker for the diagnosis of TTP, since there are several studies supporting a statistically significant decrease in ADAMTS13 in other TMAs, such as HELLP syndrome/preeclampsia [ 2 , 17 , 18 , 19 , 20 , 21 , 22 , 24 ]. ADAMTS13 activity values can vary from 12% to 43% in HELLP syndrome.…”

Section: Discussionmentioning

confidence: 99%

Molecular Advances in Preeclampsia and HELLP Syndrome

Gardikioti

Venou

Gavriilaki

et al. 2022

IJMS

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Preeclampsia (PE) constitutes one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. The circumstance typically implicates formerly healthful normotensive women, after 20 weeks of gestation, typically withinside the third trimester, without regarded threat elements or past deliveries. PE can be further complicated with hemolysis and thrombocytopenia, leading to the emergence of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low platelets). Both conditions are classified as hypertensive diseases of pregnancy (HDP), and their pathogenesis has been linked to an excessive maternal inflammatory response, accompanied by enhanced endothelial activation. Several studies have found that in pregnancies affected by PE/HELLP, von Willebrand factor (vWF) antigen levels (vWF:Ag) are significantly elevated, while its cleaving protease (ADAMTS-13, A Disintegrin-like and Metalloprotease with Thrombospondin type 1 motif, member 13) activity is normal to decreased. Furthermore, the higher urine excretion of the terminal complement complex C5b-9, as well as its greater deposition in the placental surface in preeclamptic women, imply that the utero-placental unit’s distinctive deficits are intimately tied to disproportionate complement activation. The goal of this updated evaluation is to provide the most up-to-date molecular advances in the pathophysiology of PE/HELLP syndromes. Recent medical data on vWF:Ag levels in patients with PE, ADAMTS-13, and dysregulation of the complement system, are highlighted and evaluated. Furthermore, we discuss the relationship between those entities and the progression of the disease, as well as their significance in the diagnostic process. Finally, considering the difficulties in analyzing and controlling those symptoms in pregnant women, we can provide a current diagnostic and therapeutic algorithm.

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“…не обнаружили каких-либо статистически значимых различий между физиологической беременностью и беременностью, осложненной ПЭ [51]. Также крайне противоречивы данные об активности ADAMTS-13 при ПЭ [51][52][53]. ADAMTS-13 разрушает vWF; однако недостаток металлопротеиназы у женщин с ПЭ может привести к непоправимым последствиям.…”

Section: особенности функционирования Adamts-13 и фактора фон виллебр...unclassified

Functioning of the ADAMTS-13/vWF axis and its clinical significance

Grigoreva

Gashimova

Бицадзе

et al. 2023

Akušerstvo, ginekologiâ i reprodukciâ

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Advances in biology have allowed us to substantially deepen our knowledge about hemostasis functioning both in health and disease. ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and von Willebrand factor (vWF) are components of the hemostasis system, which physiological interaction holds an important place in maintaining homeostasis. ADAMTS-13 is a metalloproteinase mainly acting to release vWF fragments into the blood plasma, as well as regulating its activity by cleaving ultra-large vWF multimers (UL-vWF) into smaller and less active forms. The study of such factors is of great clinical importance, since a decrease in ADAMTS-13 activity and an increase in vWF level can be predictors of microcirculatory disorders that play an important role in developing multiple organ failure. However, very few and fully contradictory studies devoted to the physiological aspects of the ADAMTS-13/vWF axis functioning in the mother–fetus system are available, therefore requiring to be further investigated.

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ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

Abstract: Introduction

Cited by 9 publications

References 41 publications

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study

Molecular Advances in Preeclampsia and HELLP Syndrome

Functioning of the ADAMTS-13/vWF axis and its clinical significance

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