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Objective: We compared blood-based DNA methylation levels of endoglin (ENG) and transforming growth factor beta receptor 2 (TGFβR2) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies. Methods: We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(ENG subset: n = 20 (9 cases, 11 controls); TGFβR2 subset: n = 28 (15 cases, 13 controls)]. Results: The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for ENG ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; P =.102) and TGFβR2 (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; P =.695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the ENG analytic subset revealed a trend between levels of ENG methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; P =.062). Conclusion: Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology. [ABSTRACT FROM AUTHOR]

Preeclampsia, one of four hypertensive disorders of pregnancy, has traditionally been characterized as new-onset hypertension and proteinuria developing after 20 weeks' gestation. It is, however, now understood to be a complex, progressive, multisystem disorder with a highly variable presentation and a number of potentially life-threatening complications. The American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy has refined preeclampsia diagnostic criteria accordingly, and as the disorder's pathogenesis has been more clearly defined, new targets for screening, diagnosis, prevention, and treatment have emerged. This clinical update provides a review of current practice related to preeclampsia risk assessment, prediction, and management. It discusses preeclampsia pathophysiology and points readers to valuable health care resources on the topic. [ABSTRACT FROM AUTHOR]

Aims As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism. Main methods A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with preeclampsia, were recruited in this prospective study. Using a case–control design in two groups of women, we administered a food frequency questionnaire to determine vitamin D dietary intake. Laboratory measures included serum vitamin D levels (25[OH]D), DNA methylation patterns and protein expression in placental genes regulating vitamin D metabolism (1α-hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X receptor, RXR) from placental tissue collected at delivery among those diagnosed with preeclampsia and those who remained normotensive throughout pregnancy. Key findings There were no significant differences in vitamin D dietary intake or mean serum 25[OH]D levels, although the proportion of women with deficient 25[OH]D levels was higher in the preeclampsia group (46%) than the normotensive group (20%). Placenta samples from women with preeclampsia also had increased DNA methylation of CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR. Significance Hypermethylation of key placental genes involved in vitamin D metabolism suggests uncoupling of processes that may interfere with placentation and availability of vitamin D at the maternal–fetal interface. [ABSTRACT FROM AUTHOR]

Objective. To determine the prevalence in an American Indian population of genetic variants with putative effects on endothelial function and determine whether they are associated with preeclampsia. Methods. Five genetic polymorphisms potentially related to endothelial function in the NOS3, GNB3, and DDAH1 genes were genotyped from a total of 101 cases, 198 controls, and an additional 110 population-based controls among an American Indian population. Results. The minor allele frequencies for NOS3 (rs1799983, rs3918227), GNB3 (rs5442), and DDAH1 (rs10158674, rs233115) among those with and without PE in this population were 25, 10, 5, 11, and 30%%, respectively. Although not statistically significant, the maximum risk associated with any of these SNPs was 2.22 (0.734-6.73, 95%% CI, p == 0.156) in a multivariate analysis of the A allele of the rs233115 SNP incorporated in a recessive model. Conclusion. Although endothelial dysfunction likely plays a role in the pathophysiology of PE, this study was unable to find evidence for an association between these five SNPs on three genes influencing endothelial function and PE. This may be due to insufficient power to detect an association, investigation of SNPs without linkage to risk of PE in this population or other factors. Investigation of additional SNPs in these or related genes and other populations seems warranted. [ABSTRACT FROM AUTHOR]

Citation Best LG, Nadeau M, Davis K, Lamb F, Bercier S, Anderson CM. Genetic variants, immune function, and risk of pre-eclampsia among American Indians. Am J Reprod Immunol 2012; 67: 152-159 Problem To determine the prevalence in an American Indian population of genetic variants with putative effects on immune function and determine if they are associated with pre-eclampsia (PE). Method of study In a study of 66 cases and 130 matched controls, six single nucleotide polymorphisms (SNP) with either previously demonstrated or postulated modulating effects on the immune system were genotyped. Allele frequencies and various genetic models were evaluated by conditional logistic regression in both univariate and multiply adjusted models. Results Although most genetic variants lacked evidence of association with PE, the minor allele of the CRP related, rs1205 SNP in a dominant model with adjustment for age at delivery, nulliparity, and body mass index, exhibited an odds ratio of 0.259 (95% CI of 0.08-0.81, P = 0.020) in relation to severe PE (48 cases). The allelic prevalence of this variant was 46.1% in this population. Conclusion Of the six SNPs related to immune function in this study, a functional variant in the 3′UTR of the CRP gene was shown to be associated with severe PE in an American Indian population. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of thrombophilic genetic variants in an American Indian population and determine if they are associated with preeclampsia.Methods: A total of 87 cases, 165 controls and an additional 75 population-based controls were genotyped for two thrombophilic polymorphisms.Results: The allelic prevalence of the factor V Leiden and 20210 G/A prothrombin variants in this population was 2.1% and 0.5% respectively. No statistically significant associations between these genetic variants and preeclampsia were found.Conclusion: The prevalence of thrombophilic variants is of possible public health significance for other morbidity; but perhaps not in relation to preeclampsia. [ABSTRACT FROM AUTHOR]

Regulatory process may be altered in response to the intrauterine environment, leading to the development of altered growth trajectory and disease later in life. Previously, our lab reported reduced leptin levels in pregnant hypertensive Sprague-Dawley rat dams with placental insufficiency. The purposes of this study were to investigate the relationship between leptin levels, growth and hypertension in two generations of offspring exposed to placental insufficiency. Leptin levels were significantly different only at 12 weeks in female first generation offspring (p < 0.05). Variations in postnatal body and organ weights were evident in first generation females at 3 and 12 weeks of age. There were no significant correlations with plasma leptin levels and systolic blood pressure in offspring groups at any age point. Our findings indicate that fetal exposure to maternal hypertension and hypoleptinemia is associated with altered leptin and growth patterns in mature female offspring and not perpetuated to a second generation. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the influence of reduced uteroplacental perfusion pressure on plasma leptin and placental leptin receptor expression in rats that develop hypertension in the third trimester of pregnancy. Study design: The ovarian arteries and abdominal aortae of pregnant Spragne-Dawley rats (n = 9) were constricted surgically on day 14 of gestation and were matched with sham controls. Systolic blood pressure and weight were measured biweekly. Maternal plasma leptin levels, placental leptin receptor abundance, fetal number, fetal weight, and placental weight were determined. Results: Reductions in perfusion pressure induced a significant decrease in maternal plasma leptin. Maternal systolic blood pressure and leptin receptor protein abundance was increased in the experimental group. Litter size and fetal and placental weight were significantly decreased in response to reduced perfusion pressure. Conclusion: Reduced uteroplacental perfusion pressure reduces litter size, fetal and placental weights, and maternal plasma leptin levels and increases placental expression of leptin receptors. [ABSTRACT FROM AUTHOR]