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C J M de Groot

Publications and source records attributed to C J M de Groot.

10 recordsLinked to original sources
PubMed2006

Matrix metalloproteinase-9 gene -1562C/T polymorphism mitigates preeclampsia.

Although the aetiology of preeclampsia is unknown, there is substantial evidence that it finds its roots in abnormal placentation. Prerequisites for successful placentation include trophoblast invasion, degradation and remodelling of the uterine decidual extracellular matrix, and apoptosis without thrombosis. We tested this hypothesis by analysing the effect of functional polymorphisms in the genes coding for MMP9, MMP3 and annexin A5 on the risk of preeclampsia using a case-control design. In 163 women with preeclampsia and 163 controls we studied the association with polymorphisms in the MMP9 (-1562 C/T), MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) genes using logistic regression analysis. A lower prevalence of the rare T allele of the MMP9 (-1562 C/T) polymorphism in women with preeclampsia was found (odds ratio 0.48, 95% confidence interval 0.25-0.90). The distribution of the MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) gene polymorphisms were similar in cases and controls. Our results suggest that the MMP9-1562T allele is associated with a reduced risk of preeclampsia and therefore may protect against maladaptation of the spiral arteries and decreased decidual degradation. The elevated MMP9 concentrations reported to be associated with the -1562T allele might be essential for the development of an adequate maternal-fetal interface early in pregnancy by facilitating trophoblast apoptosis and degradation.

Adult↗
PubMed2006

Mannose-binding lectin levels during pregnancy: a longitudinal study.

BACKGROUND: Pregnancy is associated with changes in the immune system. Although previous studies have focussed mainly on adaptive immunity, there are indications that components of innate immunity, such as mannose-binding lectin (MBL), are associated with pregnancy outcome. Although this would suggest that pregnancy also involves adaptations in innate immunity, there are few studies in this area. Therefore, we aimed to determine whether MBL concentrations and the following steps in complement pathway activation are influenced by pregnancy. METHODS: MBL and Ficolin-2 concentrations, MBL-MBL-associated serine protease (MASP) complex activity, MBL pathway activity and classical complement pathway activity were determined by enzyme-linked immunosorbent assay (ELISA) in sera from pregnant women (n=32) during each trimester and post-partum. MBL genotyping was performed by PCR. RESULTS: During pregnancy, MBL concentrations increased to 140% [interquartile range (IQR) 116-181%, P < 0.0001]. This increase was already present at 12 weeks of pregnancy and was most pronounced in the high-production AA-genotype. Directly Post-partum MBL concentrations dropped to 57% of baseline (IQR 44-66%, P < 0.0001). Variations in MBL levels were reflected by similar changes in the following steps of complement activation, r > 0.93 (P < 0.01). Ficolin-2 levels and classical complement pathway activity were not similarly influenced by pregnancy. CONCLUSIONS: Pregnancy and the post-partum period profoundly influence MBL serum concentration and MBL complement pathway activity.

Adult↗
PubMed2004

Interleukin 10-2849AA genotype protects against pre-eclampsia.

Recently, it has been described that human fertility is associated with the interleukin 10 (IL10) -2849 AA genotype. Pre-eclampsia is the most common pregnancy-specific complication. In the pathogenesis of pre-eclampsia, IL10 may affect maternal intravascular inflammation as well as endothelial dysfunction. Therefore, we tested the hypothesis that pre-eclampsia is associated with genetic variation in the IL10 promoter region in a case-control study for pre-eclampsia. Women homozygous for the IL10 -2849A allele have a threefold reduced risk for pre-eclampsia compared to controls (odds ratio 0.29; 95% CI 0.10-0.83). No differences in genotype frequency were found for polymorphisms in the IL10 promoter region at positions -1082, -819 and -592. This suggests that there is a genetically determined mechanism which protects the mother against pre-eclampsia, as reflected in the lower frequency of the IL10 -2849AA genotype in pre-eclamptic women.

Case-Control Studies↗
PubMed2004

Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment.

Anticoagulants↗
PubMed2004

New approach for the identification of folate-related pathways in human embryogenesis.

The role of natural folate intake and synthetic folic acid supplementation in the prevention of some congenital malformations is known, but on a molecular biological level poorly understood. In a first approach to identify folate-regulated pathways in human embryogenesis, tryptic digests of Epstein Barr Virus-immortalized B-lymphoblasts proteins from 6 cleft lip and/or palate patients and 2 controls were compared using matrix assisted laser desorption ionisation--time of flight (MALDI-TOF) mass spectrometry. After immortalisation, the lymphoblasts were cultured for 22 days in folate-rich, i.e. 5-methyltetrahydrofolate (5-mTHF), or folate-free medium. On day 22, 5-mTHF was added to the folate-free cultures and the profiles on day 22 and 23 were compared. After background correction for the peptide profiles of the folate-rich cultures, we found in the folate-free mediaseveral differentially expressed peptide peaks upon addition of 5-mTHF. These peptide peaks were mass annotated and matched withthe MSDB human database. The results suggest some folate-regulated protein candidates as Frizzled and the Rho GTP-ases WRCH and Chp that are known in human embryogenesis. Differential folate expressed proteins in patients and controls, however, have to be further investigated.

B-Lymphocytes↗
PubMed2002

[The pregnant patient with acute liver disease].

Acute liver disease was diagnosed in three pregnant patients: two 30-year-old women had a 'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome and acute fatty liver of pregnancy, respectively, and a 20-year-old woman had acute liver failure due to acute hepatitis B. The first two patients had a caesarean section, the third one delivered her child, which died spontaneously shortly after birth at a gestational age of 23 weeks. She was then treated by liver transplantation. All three patients left the hospital in good condition. Liver diseases in pregnancy may be pregnancy-related, e.g. the HELLP syndrome and acute fatty liver of pregnancy, but they may also be coincidental phenomena, e.g. viral hepatitis. The HELLP syndrome is often associated with pre-eclampsia, and presents with epigastric pain and thrombocytopenia with haemolysis. Acute fatty liver disease and acute liver failure due to hepatitis present with liver insufficiency characterised by anorexia, nausea, coagulopathy, hypoglycaemia and elevated serum ammonia levels. Management depends on the diagnosis and the gestational age; pregnancy complicated by acute fatty liver disease should be terminated while pregnancy complicated by the HELLP syndrome early in pregnancy may be maintained to improve the outcome of the foetus. In acute liver failure due to viral hepatitis, termination of pregnancy alone does not affect the disease.

Abortion, Induced↗