Alpha-foetoprotein in umbilical cord in relation to severe pre-eclampsia, birth weight and future breast cancer risk

Women born after pre-eclamptic pregnancies have been reported to be at reduced risk of breast cancer as adults, because of reduced intrauterine oestrogen influence on breast tissue; high levels of α-foetoprotein (a glycoprotein with anti-oestrogenic properties), however, could also be important. In severe pre-eclampsia, placental function and foetal growth are reduced, and umbilical cord plasma levels of α-foetoprotein could reflect the underlying processes. Umbilical cord blood was collected in 12 804 consecutive deliveries. Among 307 pregnancies with clinical pre-eclampsia, 66 singleton pregnancies were identified as clinically severe, and 610 singleton pregnancies were selected as controls. Oestradiol and α-foetoprotein were measured from umbilical plasma, and birth weight was standardized as the ratio between the observed and expected birth weight, adjusted for differences in gestation length and offspring sex. Cord plasma levels of α-foetoprotein were significantly higher in severe pre-eclampsia than controls (P<0.01) after adjustment for gestational age and birth weight. For oestradiol, there was no difference in cord plasma levels between the severe pre-eclampsia group and controls, after adjustment for length of gestation and birth weight. These results suggest that an anti-oestrogenic effect associated with pre-eclampsia may be mediated through high levels of α-foetoprotein rather than low levels of oestradiol

A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)

The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (ncases= 1135, ncontrols= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases

Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene

Miira Klemetti ja Anna Inkeri Lokki FINNPEC Study Group'n jäseniä. Jäseniä yht. 16.Peer reviewe

Insulin-like growth factors and foetal programming--a workshop report

C. T. Roberts, J. A. Owens, A. M. Carter, J. E. Harding, R. Austgulen and M. Wlode

Apoptosis may underlie the pathology of zinc-deficient skin

The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenerative changes within keratinocytes. Despite the well-documented association between zinc deficiency and skin pathology, it is not clear which cellular processes are most sensitive to zinc deficiency and could account for the typical pathological features. We used the cultured HaCaT keratinocyte line to obtain insight into the cellular effects of zinc deficiency, as these cells show many characteristics of normal skin keratinocytes. Zinc deficiency was induced by growing cells in the presence of the zinc chelator, TPEN, or by growth in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a 44% reduction of intracellular zinc levels and a 75% reduction in the activity of the zinc-dependent enzyme, 5\u27-nucleotidase, relative to the control cells. Over a period of 7 days of exposure to zinc-deficient conditions, no changes in cell viability and growth, or in the cytoskeletal and cell adhesion systems, were found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by the presence of DNA fragmentation and expression of active caspase-3 in cells. These results demonstrate that apoptosis is the earliest detectable cellular change induced by zinc deficiency in HaCaT keratinocytes. Our observations account for many of the features of zinc deficiency, including the presence of degenerate nuclei, chromatin aggregates and abnormal organization of keratin, that may represent the later stages of apoptosis. In summary, a major causal role for apoptosis in the pathology of zinc deficiency in the skin is proposed. This role is consistent with the previously unexplained diverse range of degenerative cellular changes seen at the ultrastructural level in zinc-deficient keratinocytes.<br /

Genetic association of preeclampsia to the inflammatory response gene SEPS1

Objective: The objective of the study was to test for a genetic association between the G-105A promoter polymorphism of the inflammatory mediator Selenoprotein S (SEPS1) and preeclampsia. Study Design: A retrospective study in a large Norwegian case-control cohort compared maternal genotype and allele frequencies of the SEPS1 g.-105G&gt;A polymorphism genotyped by SNPlex assay in preeclamptic (n = 1139) and control (n = 2269) women. Statistical significance was determined by ?2 and multivariate regression analyses. Results: Women with preeclampsia were 1.34 times more likely to have the GA or AA genotype (P = .0039; 95% confidence interval [CI] 1.09 to 1.64) and 1.22 times more likely to carry the A allele (P = .023; odds ratio, 1.22; 95% CI, 1.02 to 1.46). Conclusion: The A allele of the SEPS1-105G&gt;A polymorphism is a significant risk factor for preeclampsia in this population. © 2008 Mosby, Inc. All rights reserved