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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined whether polymorphisms in the promoter region of the tumour necrosis factor alpha (TNF-alpha) gene contributes to differences in susceptibility to develop pre-eclampsia. The study involved 133 pre-eclamptic and 115 healthy pregnant women who were genotyped for the G-308A polymorphism of the TNF-alpha gene. The frequency of the G-308A allele was more common in the pre-eclampsia group than among the controls (P=0.046), giving an odds ratio of 0.57 (95% CI: 0.32-0.99), but there were no differences in the genotype distribution. The data from the G-308A polymorphism was combined with the previously published genotype and allele data from the C-850T polymorphism of the TNF-alpha gene, and used to assess a haplotype estimation analysis. Estimated overall pair of loci haplotype frequencies differed significantly between the groups (P=0.023+/-0.004). In the single haplotype association analysis, the haplotype C-A versus others was over-represented in the pre-eclampsia group (P=0.041+/-0.003), whereas the haplotype T-G versus others was less common in the pre-eclampsia group (P=0.035+/-0.003), compared with the controls. In conclusion, the polymorphisms of the TNF-alpha gene showed a significant haplotype association with susceptibility to pre-eclampsia in the Finnish population.
Mol Hum Reprod 2005 Jun
PMID:Tumour necrosis factor-alpha gene haplotype is associated with pre-eclampsia. 1590 45

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.
Blood Cells Mol Dis
PMID:Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia. 1590 8

Located in the principal cells of the collecting duct, aquaporin-2 (AQP2) is responsible for the regulated water reabsorption in the kidney and is indispensable for the maintenance of body water balance. Disregulation or malfunctioning of AQP2 can lead to severe diseases such as nephrogenic diabetes insipidus, congestive heart failure, liver cirrhosis and pre-eclampsia. Here we present the crystallization of recombinantly expressed human AQP2 into two-dimensional protein-lipid arrays and their structural characterization by atomic force microscopy and electron crystallography. These crystals are double-layered sheets that have a diameter of up to 30 microm, diffract to 3 A(-1) and are stacked by contacts between their cytosolic surfaces. The structure determined to 4.5 A resolution in the plane of the membrane reveals the typical aquaporin fold but also a particular structure between the stacked layers that is likely to be related to the cytosolic N and C termini.
J Mol Biol 2005 Jul 08
PMID:The 4.5 A structure of human AQP2. 1592 55

The pleiotropic effects of human chorionic gonadotrophin (hCG), the key regulator of human pregnancy, are dependent upon cell surface expression of its functional cognate receptor LHCGR in the placental trophoblasts, corpus luteum, uterus, vascular endothelial and smooth muscle cells. Additionally, lutenizing hormone-mediated signalling failure has often been linked to activating/inactivating mutations in LHCGR. One of the intriguing aspects of these studies is that the mutations are most frequently located within C-terminal 200-350 residues of the receptor protein. In an attempt to reconcile the mechanistic basis of LHCGR regulation and mutations, we have carried out bioinformatic analyses to identify the CpG-rich regions and the major potential scaffold/matrix attachment sites (S/MARs) in LHCGR and neighbouring gene (ALF) at human chromosome 2p21. Based on these analyses, we propose a chromatin-loop model, which may explain the temporal regulation and susceptibility to mutation of the human LHCGR. One of the characteristic features of the model, is that the major potential S/MAR sequences of the human LHCGR gene (68 kb) are located at the 3' end of the gene, and unlike mouse, the transmembrane and C-terminal protein coding sequences at exon 11 are embedded in this S/MAR site. Moreover, this region is subject to antisense transcription from the neighbouring gene ALF, which is gonad-specific and is only activated in meiotic spermatocytes and oocytes. Together, these analyses suggest that exon 11 of human LHCGR could be more susceptible to mutation than the other 10 exons together and that activation of LHCGR, contingent to the somatic silencing of neighbouring ALF, could be linked to male-limited precocious puberty and pre-eclampsia.
Mol Cell Endocrinol 2005 Sep 28
PMID:Natural antisense LHCGR could make sense of hypogonadism, male-limited precocious puberty and pre-eclampsia. 1608 88

Pre-eclampsia/eclampsia is a serious disorder of human pregnancy that has a worldwide incidence of 2-10% and carries a severe morbidity and mortality risk for both mother and child. Its precise cause remains unknown. However, there is increasing evidence of an underlying complex maternal genetic susceptibility. Its high population incidence in the face of strong negative selection pressure suggests that the gene(s) involved have a selective advantage and/or a high mutation rate. One class of genetic diseases that involve a high mutation rate are the trinucleotide repeat expansion diseases. Thus, the aim of this study was to determine whether there is an association between a trinucleotide (CAG) repeat expansion and pre-eclampsia/eclampsia. We have used the repeat expansion detection (RED) method, which was developed to directly identify clinically significant repeat expansions, to analyse genomic DNA from an Australian and New Zealand population. The maximal CAG repeat length for each individual was recorded and the Mann-Whitney U and Wilcoxon rank sum test for independent samples were used to compare distributions for CAG/CTG repeats between two populations. There were no statistically significant differences between the distribution of CAG repeats in normotensive (n = 59) and severe pre-eclampsia (n = 69) (Mann-Whitney U = 1732; P = 0.14), and normotensive (n = 59) and eclamptic (n = 15) populations (Mann-Whitney U = 417, P = 0.726). Therefore, these RED results do not support a role for a large CAG expansion in pre-eclampsia/eclampsia. However, these data do not preclude the possibility that a small CAG expansion is associated with the disorder nor do they negate the hypothesis that a highly mutable gene contributes to the genetic component of pre-eclampsia/eclampsia.
Mol Hum Reprod 2005 Jul
PMID:Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method. 1612 75

To analyze the polymorphism of TAP gene and the shared rates of alleles between mothers and their infants in Chinese patients with pre-eclampsia, TAP1 and TAP2 genotyping was performed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 42 patients, 106 normal pregnant women, and their neonates. The allelic frequency of TAP and the alleles shared in maternal-fetus were compared and analyzed in the two groups. Our results showed that, with totally eight alleles of TAP1 and TAP2 examined in the samples, no significant difference was found in allelic frequencies between pre-eclampsia group and control group, as well as between mothers and their neonates. Similar finding was obtained in the comparison with shared alleles. In conclusion, our results do not support a role for the polymorphisms of TAP in the etiology of pre-eclampsia.
Cell Mol Immunol 2005 Apr
PMID:Analysis of TAP1 and TAP2 polymorphism of mother-infant in Chinese patients with pre-eclampsia. 1619 21

Available data indicate that progesterone is able to treat pregnancy-induced hypertension (preeclampsia). Dydrogesterone and 17alpha-hydroxyprogesterone caproate might also be used for this purpose. Prevention of hypertensive disorders in preeclampsia also seems possible, but studies are needed to confirm this.
J Steroid Biochem Mol Biol 2005 Dec
PMID:Prevention and treatment of pregnancy-induced hypertension (preeclampsia) with progestogens. 1623 93

Preeclampsia is a multisystemic pregnancy-associated disease affecting about 3-7% of pregnancies worldwide and is still a principal cause of fetal and maternal morbidity and mortality. To identify potential markers, we have compared gene expression profiles from control and preeclamptic placental tissues taken at various age-matched gestational stages using complementary DNA microarray analysis. Besides previously identified preeclampsia-associated genes, novel differentially expressed transcripts were found. The soluble form of the disintegrin metalloprotease ADAM 12 (a disintegrin and metalloproteinase 12; meltrin-alpha) represented the most upregulated transcript. This was confirmed by in situ hybridization of sections of preeclamptic placentas and by serum protein analysis of preeclamptic pregnant women. Thus, ADAM 12 could serve as an early biomarker for preeclampsia that may be of predictive and/or functional significance.
J Mol Med (Berl) 2005 Nov
PMID:Preeclampsia: increased expression of soluble ADAM 12. 1623 73

Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1alpha and HIF2alpha, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIFalpha and HIFbeta (ARNT) subunits. Placentas from Arnt-/- and Hif1alpha-/- Hif2alpha-/- embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hifalpha, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, and cell fate decisions, demonstrating that O2 tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia.
Mol Cell Biol 2005 Dec
PMID:Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. 1628 60

HLA-G is thought to play a key role in implantation by modulating cytokine secretion to control trophoblast invasion and to maintain a local immunosuppressive state. It differs from other class I molecules in that the gene can be alternatively spliced to produce four membrane-bound (G1, G2, G3 and G4) and three soluble isoforms (G5, G6 and G7). The soluble isoforms have recently attracted attention as their levels may be diagnostic of poor trophoblast invasion in miscarriage or pre-eclampsia and the implantation potential of IVF embryos. Although the expression and function of HLA-G2, G3, G4 and G7 has previously been a matter of debate, until now it has been generally accepted that soluble HLA-G5 and HLA-G6 are both expressed and secreted by trophoblast. However, Blaschitz et al. (2005) have reinvestigated this question and come to the surprising conclusion that they are not. They have shown that trophoblast only expresses the membrane-bound HLA-G1 isoform and not soluble HLA-G5 and -G6. Furthermore, although soluble HLA-G could be found in trophoblast culture supernatants, it appears not to be derived by alternative splicing but by the cleavage of HLA-G1. The source of the soluble HLA-G may not matter from a diagnostic perspective, but these findings, if confirmed, have important implications for our understanding of the biology of HLA-G.
Mol Hum Reprod 2005 Oct
PMID:Does 'soluble' HLA-G really exist? Another twist to the tale. 1633 Apr 68


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