Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family

Dijk, Marie van; Mulders, Joyce; Poutsma, Ankie; Könst, Andrea A.M.; Lachmeijer, Augusta M. A.; Dekker, Gustaaf A.; Blankenstein, Marinus A.; Oudejans, Cees B.M.

doi:10.1038/ng1541

Cited by 210 publications

(192 citation statements)

References 29 publications

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“…A recent study indicates expression of highly polymorphic genes relevant to implantation with missense mutations cosegregating with preeclampsia in a chromosomal site identified as related to preeclampsia in Dutch studies. 57 Interestingly, most of the preeclampsia gene candidates are not localized to these sites. These studies support the heterogeneity of preeclampsia and its multifactorial inheritance.…”

Section: Maternal Fetal/placental Interactions In Preeclampsiamentioning

confidence: 99%

Preeclampsia

2005

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Abstract-Preeclampsia is a pregnancy complication with serious consequences for mother and infant. The disorder is diagnosed by gestational hypertension and proteinuria but is far more than pregnancy induced hypertension. Preeclampsia is proposed to occur in 2 stages. Key Words: preeclampsia Ⅲ hypertension, pregnancy Ⅲ oxidative stress Ⅲ endothelium P reeclampsia is a pregnancy complication recognized by new-onset gestational hypertension and proteinuria (see definitions below). The disorder affects both mothers and their infants. Once the disease is evident clinically, it can be cured only by delivery. In developed countries, surveillance for preeclampsia through prenatal care allows for early identification and intervention via delivery. This management has changed little in the last 100 years, and it is very effective at reducing maternal mortality. However, maternal morbidity remains great with preeclampsia, which continues to be one of the leading causes for the admission of pregnant women to intensive care units in the developed world. 1 Furthermore, fetal mortality and morbidity is considerable, related to the effects of the disease on the fetus as well as prematurity. The indicated delivery of women to prevent the progression of preeclampsia is responsible for 15% of all preterm births. 2 In developing countries, where inadequate prenatal care limits preeclampsia surveillance, maternal mortality is common, accounting for 50 000 deaths yearly. 3 The hypertensive disorders of pregnancy include hypertension that antedates pregnancy, chronic hypertension, and gestational hypertension occurring uniquely during pregnancy. When the gestational hypertension is accompanied by new-onset proteinuria, the disorder is termed preeclampsia, and when not associated with proteinuria, transient hypertension of pregnancy. If the woman with chronic hypertension also manifests evidence of preeclampsia, this is classified chronic hypertension with superimposed preeclampsia. Eclampsia is the occurrence of seizures in women with preeclampsia. 4 These criteria have been extraordinarily useful to aid in recognizing pregnant women at risk. Greatest risk for mother and baby is present with preeclampsia, and the risk for chronic hypertensive pregnancy is primarily with superimposed preeclampsia. However, the attention to hypertension has, for many years, limited research attention to primarily mechanisms of hypertension. This has not been helpful. In the last 2 decades, appreciation that preeclampsia is a multisystemic syndrome characterized by vasoconstriction, metabolic changes, endothelial dysfunction, activation of the coagulation cascade, and increased inflammatory response, to mention only some of the organ systems involved, has redirected research. 5 As a result, progress in understanding the disorder has accelerated greatly, with attendant optimism for potentially effective treatments. 5 In this article, we consider this recent progress and its clinical implications.

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Section: Maternal Fetal/placental Interactions In Preeclampsiamentioning

confidence: 99%

Preeclampsia

2005

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“…Linked loci have been found on chromosomes 2 (2p13 (15,16) and 10 (10q22q22 (17)) but to date no specific genes in the linked loci have been implicated in causing the problem. However, changes in the expression of several genes in the placenta have been proposed to affect the development of PE.…”

Section: Introductionmentioning

confidence: 99%

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes

Centlow

Carninci²,

Nemeth

et al. 2008

Fertility and Sterility

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Using microarrays made with cDNAs from subtracted placental libraries, we show increased hemoglobin production in the preeclamptic placenta. Heme and hemoglobin may cause endothelial damage and inflammation and drive pathological changes in the placenta if they are released there. Study Objective:To create a library enriched in cDNAs from preeclamptic placentas to print on to microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies. Design: Prospective study.Setting: University women's clinic and academic research laboratory.Patients: Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.Interventions: Placenta and placenta bed biopsies were collected after delivery. Main Outcome Measures:Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time PCR and histologically using in situ hybridization and immunohistochemistry.Results: 30 genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative rt-PCR. Hemoglobin α2 and γ transcripts were significantly over-expressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin-chains. Conclusions:We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins which cause endothelial damage and inflammation.

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“…Le lecteur intéressé par la question pourra se référer au papier de Leonardo Fainboim (BuenosAires, Argentine) à paraître dans le prochain numéro spécial du JRI. le premier découvert par ce type d'approche, sur un sous-échantillon limité de familles nucléaires de femmes prééclamp-tiques hollandaises [44]. L'implication de STOXI dans la pathologie est controversée, néanmoins, des résultats récents montrent une très bonne corrélation entre les effets transcriptionnels de ce facteur et ceux observés dans les prééclampsies tout-venant.…”

Section: Problème En Débat Actuellement : Le Phénomène De Mémoire Immunclassified

Débats actuels sur l’immunologie de la prééclampsie. Comptes rendus du sixième colloque international de La Réunion (décembre 2008)

Robillard

Chaouat

Bouteiller

et al. 2009

Gynécologie Obstétrique & Fertilité

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RésuméLes troubles hypertensifs de la grossesse (THG) représentent globalement 10 % des naissances humaines, et leur complication majeure, la prééclampsie, 3 à 5 %. L'étiologie de ces THG reste toujours controversée ; cependant des avancées majeures ont eu lieu ces dernières 25 années. Le « sixième colloque international d'immunologie de la reproduction, de l'immunotolérance et de l'immunologie de la prééclampsie » 2008 a fêté cette année son dixième anniversaire. Durant cette décennie, ces six colloques bisannuels ont largement contribué à nourrir le débat entre immunologistes, cliniciens, anthropologues et spécialistes des maladies cardiovasculaires. Le défaut de l'invasion trophoblastique profonde obligatoire chez les humains rencontrée dans la prééclampsie, le retard de croissance intra-utérin, et dans une certaine mesure dans la menace d'accouchement prématuré n'ont été compris qu'à la fin des années 1970. Dans le même temps, des études cliniques et épidémiologiques à la fin du XX e siècle ont permis de réaliser que la prééclampsie « maladie des primipares » pouvait en fait être une maladie de la première grossesse au niveau d'un couple. Parmi les avancées significatives, l'immunologie de la reproduction a fait des bonds de géant dans la dernière décennie. Ce papier relate les étapes majeures franchies dans la compréhension de cette pathologie et met en lumière l'intérêt de ces travaux immunologiques et des nouveaux concepts afférents. Il semble, en ce début de XXI e siècle que nous soyons plus près que jamais de comprendre l'étiologie de cette énigme obstétricale. Dans ce domaine, l'immunologie de la reproduction sera sans doute un des interlocuteurs majeurs. Mots clés : Prééclampsie ; épidémiologie ; immunologie AbstractHypertensive disorders of pregnancy (HDP) represent globally 10% of human births and their major complication, preeclampsia, 3 to 5%. The etiology of these HDP remains still uncertain, however major advances have been made these last 25

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Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family

Cited by 210 publications

References 29 publications

Preeclampsia

Preeclampsia

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes

Débats actuels sur l’immunologie de la prééclampsie. Comptes rendus du sixième colloque international de La Réunion (décembre 2008)

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