Dataset Information

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators.

ABSTRACT: The study represents the first comprehensive analysis of Stanniocalcin-1 (STC1) hormone in human pregnancy, assessing clinical, lifestyle, and genetic determinants of circulating STC1 at term.Participants included women with (n = 50) and without (n = 316) preeclampsia (PE) at delivery, recruited in the REPROgrammed fetal and/or maternal METAbolism (REPROMETA) study (2006-2011, Estonia). Genetic association analysis combined PE cases (n = 597) and controls (n = 623) from the REPROMETA and Finnish Genetics of Preeclampsia Consortium (2008-2011) studies.Maternal postpartum plasma STC1 was measured by ELISA (n = 366) and placental STC1 gene expression by TaqMan quantitative RT-PCR (n = 120). Genotyping was performed using Sequenom MassArray.Significantly higher STC1 plasma level was measured for the PE (median, 1952 pg/mL; 1030-4284 pg/mL) compared with non-PE group (median, 1562 pg/mL; 423-3781 pg/mL; P = 3.7 × 10-4, Mann-Whitney U test). Statistical significance was enhanced after adjustment for cofactors (linear regression, P = 1.8 × 10-6). STC1 measurements were negatively correlated with maternal smoking. Prepregnancy body mass index had a positive correlation with STC1 only among PE patients (r = 0.45; P = .001). The strongest genetic association with hormone concentrations was detected for STC1 single nucleotide polymorphisms rs3758089 (C allele: minor allele frequency, 5%; linear regression: ? = 249.2 pg/mL; P = .014) and rs12678447 (G allele: minor allele frequency, 7%; ? = 147.0 pg/mL; P = .082). rs12678447 placental genotypes were significantly associated with STC1 gene expression (P = .014). The REPROMETA/Finnish Genetics of Preeclampsia Consortium meta-analysis suggested an increased risk to develop late-onset PE for the rs12678447 G allele carriers (P = .05; odds ratio = 1.38 [0.98-1.93]).Increased STC1 hormone represents a hallmark of late-onset PE. STC1 gene variants modulate placental gene expression and maternal hormone levels.

SUBMITTER: Juhanson P

PROVIDER: S-EPMC5155696 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators.

Juhanson Peeter P Rull Kristiina K Kikas Triin T Laivuori Hannele H Vaas Pille P Kajantie Eero E Heinonen Seppo S Laan Maris M

The Journal of clinical endocrinology and metabolism 20160907 12

<h4>Context and objectives</h4>The study represents the first comprehensive analysis of Stanniocalcin-1 (STC1) hormone in human pregnancy, assessing clinical, lifestyle, and genetic determinants of circulating STC1 at term.<h4>Design, setting, and participants</h4>Participants included women with (n = 50) and without (n = 316) preeclampsia (PE) at delivery, recruited in the REPROgrammed fetal and/or maternal METAbolism (REPROMETA) study (2006-2011, Estonia). Genetic association analysis combined ...[more]

PMID: 27603899

Similar Datasets

Project description:BackgroundWhile preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study's purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls).ResultsIn the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×10-8, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×10-5. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample.ConclusionsThe discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1-2 and significant DMRs that were not examined in the replication phase.

Project description:BackgroundAlthough preeclampsia has long been recognized as a condition affecting late pregnancy, little is known of its pathogenesis or treatment. The placenta releases a number of hormones and molecules that influence the course of pregnancy, one of which is chromogranin A, a soluble protein secreted mainly from the chromaffin cells of the adrenal medulla. Its role in pregnancy and pregnancy-related disorders remains unclear. Therefore, the main aim of the proposed study is to determine whether chromogranin A is related with the occurrence of preeclampsia.MethodsPlacental samples were collected from 102 preeclamptic patients and 103 healthy controls, and Chromogranin A gene (CHGA) expression was measured using real-time RT-PCR, The RT-PCR results were verified on the protein level using ELISA. The normal distribution of the data was tested using the Shapiro-Wilk test. The clinical and personal characteristics of the groups were compared using the Student's t-test for normally-distributed data, and the χ2 test for categorical variables. The Mann-Whitney U test was used for non-normally distributed data. As the log- transformation was not suitable for the given outcomes, the Box- Cox Transformation was used to normalize data from ELISA tests and CHGA expression. Values of P < .05 were considered statistically significant.ResultsChromogranin A gene expression was found to be significantly higher in the study group than in controls. Protein analyses showed that although the CgA concentration in placental samples did not differ significantly, the catestatin (CST) level was significantly lower in samples obtained from women with preeclampsia, according to the controls.Conclusions for practiceThis study for the first time reveals that chromogranin A gene expression level is associated with preeclampsia. Moreover, the depletion in catestatin level, which plays a protective role in hypertension development, might be a marker of developing preeclampsia. Further studies may unravel role of Chromogranin A in the discussed disease.

Project description:Preeclampsia (PE) is a complication of pregnancy characterized by hypertension (HTN-Preg), and often proteinuria. If not managed promptly, PE could lead to eclampsia and seizures. PE could also lead to intrauterine growth restriction (IUGR) and prematurity at birth. Although PE is a major cause of maternal and fetal morbidity and mortality, the underlying mechanisms are unclear. Also, there is a wide variability in the incidence of PE, ranging between 2 and 8% of pregnancies in the Eastern, Western and Developing world, suggesting regional differences in the risk factors and predictors of the pregnancy-related disorder. Several demographic, genetic, dietary and environmental factors, as well as maternal circulating biomarkers have been associated with PE. Demographic factors such as maternal race and ethnicity could play a role in PE. Specific genetic polymorphisms have been identified in PE. Maternal age, parity, education and socioeconomic status could be involved in PE. Dietary fat, protein, calcium and vitamins, body weight, and environmental factors including climate changes and air pollutants could also play a role in PE. Several circulating cytoactive factors including anti-angiogenic factors and cytokines have also been associated with PE. Traditional midwifery care is a common practice in local maternity care units, while advanced perinatal care and new diagnostic tools such as uterine artery Doppler velocimetry have been useful in predicting early PE in major medical centers. These PE risk factors, early predictors and diagnostic tools vary vastly in different regions of the Eastern, Western and Developing world. Further understanding of the differences in the demographic, genetic, dietary and environmental factors among pregnant women in different world regions should help in designing a region-specific cluster of risk factors and predictors of PE, and in turn provide better guidance for region-specific tools for early detection and management of PE.

Dataset Information

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators.

Publications

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets