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

CONTEXT AND OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: Participants included women with (n = 50) and wi...

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Autores principales: Juhanson, Peeter, Rull, Kristiina, Kikas, Triin, Laivuori, Hannele, Vaas, Pille, Kajantie, Eero, Heinonen, Seppo, Laan, Maris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155696/
https://www.ncbi.nlm.nih.gov/pubmed/27603899
http://dx.doi.org/10.1210/jc.2016-1873
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author Juhanson, Peeter
Rull, Kristiina
Kikas, Triin
Laivuori, Hannele
Vaas, Pille
Kajantie, Eero
Heinonen, Seppo
Laan, Maris
author_facet Juhanson, Peeter
Rull, Kristiina
Kikas, Triin
Laivuori, Hannele
Vaas, Pille
Kajantie, Eero
Heinonen, Seppo
Laan, Maris
author_sort Juhanson, Peeter
collection PubMed
description CONTEXT AND OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOME MEASURE(S): 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. RESULTS: 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: β = 249.2 pg/mL; P = .014) and rs12678447 (G allele: minor allele frequency, 7%; β = 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]). CONCLUSIONS: Increased STC1 hormone represents a hallmark of late-onset PE. STC1 gene variants modulate placental gene expression and maternal hormone levels.
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spelling pubmed-51556962016-12-28 Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators Juhanson, Peeter Rull, Kristiina Kikas, Triin Laivuori, Hannele Vaas, Pille Kajantie, Eero Heinonen, Seppo Laan, Maris J Clin Endocrinol Metab Original Articles CONTEXT AND OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOME MEASURE(S): 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. RESULTS: 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: β = 249.2 pg/mL; P = .014) and rs12678447 (G allele: minor allele frequency, 7%; β = 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]). CONCLUSIONS: Increased STC1 hormone represents a hallmark of late-onset PE. STC1 gene variants modulate placental gene expression and maternal hormone levels. Endocrine Society 2016-12 2016-09-07 /pmc/articles/PMC5155696/ /pubmed/27603899 http://dx.doi.org/10.1210/jc.2016-1873 Text en https://creativecommons.org/licenses/by-nc/4.0/ This article is published under the terms of the Creative Commons Attribution-Non Commercial License (CC-BY-NC; https://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Original Articles
Juhanson, Peeter
Rull, Kristiina
Kikas, Triin
Laivuori, Hannele
Vaas, Pille
Kajantie, Eero
Heinonen, Seppo
Laan, Maris
Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title_full Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title_fullStr Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title_full_unstemmed Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title_short Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators
title_sort stanniocalcin-1 hormone in nonpreeclamptic and preeclamptic pregnancy: clinical, life-style, and genetic modulators
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155696/
https://www.ncbi.nlm.nih.gov/pubmed/27603899
http://dx.doi.org/10.1210/jc.2016-1873
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