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



Increased STC1 hormone represents a hallmark of late-onset PE. STC1 gene variants modulate placental gene expression and maternal hormone levels.
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Peeter
P
Juhanson
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Kristiina
K
Rull
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Triin
T
Kikas
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Hannele
H
Laivuori
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Pille
P
Vaas
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Eero
E
Kajantie
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Seppo
S
Heinonen
Human Molecular Genetics Research Group (P.J., K.R., T.K., M.L.), Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynaecology (K.R., P.V.), University of Tartu, and Women's Clinic of Tartu University Hospital (K.R., P.V.), Tartu 51014, Estonia; Medical and Clinical Genetics (H.L.), University of Helsinki and Helsinki University Hospital, and Institute for Molecular Medicine Finland (H.L.), University of Helsinki, FIN-00014 Helsinki, Finland; Obstetrics and Gynecology (H.L., S.H.) and Children's Hospital (E.K.), Helsinki University Hospital and University of Helsinki, FIN-00029 Helsinki, Finland; Chronic Disease Prevention Unit (E.K.), National Institute for Health and Welfare, FIN-00271 Helsinki, Finland; Research Unit of Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology, Ophtalmology (E.K.), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90014 Oulu, Finland; and Institute of Biomedicine and Translational Medicine (M.L.), University of Tartu, Tartu 50411, Estonia.
Maris
M
Laan
D000328:Adult; D016022:Case-Control Studies; D004957:Estonia; D005260:Female; D005387:Finland; D015870:Gene Expression; D056726:Genetic Association Studies; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics; D011247:Pregnancy / Q000097:blood*; D055815:Young Adult
D006023:Glycoproteins; C051795:teleocalcin