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677 C-->T polymorphism of the methylenetetrahydrofolate reductase gene and preeclampsia.

https://arctichealth.org/en/permalink/ahliterature197794
Source
Obstet Gynecol. 2000 Aug;96(2):277-80
Publication Type
Article
Date
Aug-2000
Author
H. Laivuori
R. Kaaja
O. Ylikorkala
T. Hiltunen
K. Kontula
Author Affiliation
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. hannele.laivuori@pp.fimnet.fi
Source
Obstet Gynecol. 2000 Aug;96(2):277-80
Date
Aug-2000
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Amino Acid Substitution
Case-Control Studies
DNA Primers
Female
Finland
Gene Expression Regulation, Enzymologic
Gene Frequency
Genotype
Heterozygote
Humans
Methylenetetrahydrofolate Reductase (NADPH2)
Oxidoreductases Acting on CH-NH Group Donors - genetics
Polymerase Chain Reaction
Polymorphism, Genetic
Pre-Eclampsia - enzymology - genetics
Pregnancy
Abstract
To evaluate C to T substitution at nucleotide 677 of N(5), N(10)-methylenetetrahydrofolate reductase gene in women with prior preeclamptic or normotensive pregnancies.
Methylenetetrahydrofolate reductase genotypes were determined in 113 Finnish women with preeclamptic first pregnancies and 103 controls with one or more normotensive pregnancies, using polymerase chain reaction and restriction enzyme analysis. Preeclampsia was defined as severe in 100 women who fulfilled one or more of the subsequent criteria: systolic blood pressure (BP) at least 160 mmHg, diastolic BP at least 110 mmHg, or proteinuria at least 2 g per 24-hour urine collection.
There were no significant differences in prevalences of the methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) between groups (57%, 40%, and 3% in the preeclamptic group and 54%, 39%, and 7%, respectively, in controls). The frequency of the T677 allele was 0.23 in the preeclamptic group and 0.26 in the control group (difference 0.03; 95% confidence interval -0.08, 0.14; P =.51). Our sample had 60% power to detect a difference of the allele frequencies similar to that (0.12) reported previously. The result was similar when analysis was restricted to patients with severe preeclampsia (T677 allele frequency 0.22).
A carrier status for the T677 allele of the methylenetetrahydrofolate reductase gene does not predispose to preeclampsia, at least in the Finnish population.
PubMed ID
10908777 View in PubMed
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Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials.

https://arctichealth.org/en/permalink/ahliterature119203
Source
BJOG. 2013 Jan;120(1):64-74
Publication Type
Article
Date
Jan-2013
Author
P M Villa
E. Kajantie
K. Räikkönen
A-K Pesonen
E. Hämäläinen
M. Vainio
P. Taipale
H. Laivuori
Author Affiliation
Research Programmes Unit, Women's Health, University of Helsinki, Helsinki, Finland. pia.villa@helsinki.fi
Source
BJOG. 2013 Jan;120(1):64-74
Date
Jan-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aspirin - therapeutic use
Double-Blind Method
Female
Finland
Humans
Platelet Aggregation Inhibitors - therapeutic use
Pre-Eclampsia - prevention & control - ultrasonography
Pregnancy
Pregnancy, High-Risk
Randomized Controlled Trials as Topic
Treatment Outcome
Ultrasonography, Doppler, Color
Young Adult
Abstract
To study the effect of aspirin in the prevention of pre-eclampsia in high-risk women.
Randomised, double-blinded, placebo-controlled trial.
Maternity clinics in ten Finnish hospitals participating in the PREDO Project.
A total of 152 women with risk factors for pre-eclampsia and abnormal uterine artery Doppler velocimetry.
Participants were randomised to start either aspirin 100 mg/day or placebo at 12 + 0 to 13 + 6 weeks + days of gestation. Because of the limited power of this trial, we also conducted a meta-analysis of randomised controlled trials that included data on 346 women with abnormal uterine artery Doppler flow velocimetry, and aspirin 50-150 mg/day started at or before 16( ) weeks of gestation.
Pre-eclampsia, gestational hypertension and birthweight standard deviation (SD) score. Outcome measures for the meta-analysis were pre-eclampsia, severe pre-eclampsia, preterm (diagnosed
Notes
Comment In: BJOG. 2013 May;120(6):774-523565954
Comment In: BJOG. 2013 May;120(6):773-423565953
Comment In: BJOG. 2013 May;120(6):77323565952
PubMed ID
23126307 View in PubMed
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Blood pressure levels but not hypertensive complications have increased in Type 1 diabetes pregnancies during 1989-2010.

https://arctichealth.org/en/permalink/ahliterature114036
Source
Diabet Med. 2013 Sep;30(9):1087-93
Publication Type
Article
Date
Sep-2013
Author
M M Klemetti
K. Teramo
M. Nuutila
M. Tikkanen
V. Hiilesmaa
H. Laivuori
Author Affiliation
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland.
Source
Diabet Med. 2013 Sep;30(9):1087-93
Date
Sep-2013
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Cohort Studies
Diabetes Mellitus, Type 1 - complications - epidemiology
Female
Finland - epidemiology
Follow-Up Studies
Health Transition
Hospitals, University
Hospitals, Urban
Humans
Hypertension - complications - epidemiology - prevention & control
Hypertension, Pregnancy-Induced - epidemiology - prevention & control
Middle Aged
Obesity - complications - epidemiology
Overweight - complications - epidemiology
Pre-Eclampsia - epidemiology - prevention & control
Pregnancy
Pregnancy Complications, Cardiovascular - epidemiology
Pregnancy in Diabetics - epidemiology
Prehypertension - complications - epidemiology
Young Adult
Abstract
The pre-pregnancy BMI and the third trimester HbA(1c) levels increased in Finnish parturients with Type 1 diabetes during 1989-2008. The aim of the present study was to investigate whether these trends have been accompanied by increases in blood pressure or hypertensive complications. Hypertension trends were analysed using the definitions of hypertension of both the American College of Obstetricians and Gynecologists and the American Diabetes Association. The associations of hypertension, as defined by the latter criteria, with perinatal complications were also studied.
The records of a cohort of 1007 consecutive patients with Type 1 diabetes with a singleton live childbirth during 1989-2010 at the Helsinki University Central Hospital were studied.
The frequencies of hypertensive pregnancy complications did not change, but the mean diastolic blood pressure increased in normotensive parturients in all trimesters. The proportion of patients with systolic blood pressure > 130 mmHg or diastolic blood pressure > 80 mmHg in the first, second and third trimesters of pregnancy increased from 25 to 33%, from 26 to 35% and from 57 to 71%, respectively. Systolic blood pressure of 131-139 mmHg or diastolic blood pressure of 81-89 mmHg in the third trimester was associated with umbilical artery pH
PubMed ID
23659525 View in PubMed
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Complement factor H variant Y402H is not a risk factor for preeclampsia in the Finnish population.

https://arctichealth.org/en/permalink/ahliterature154303
Source
Hypertens Pregnancy. 2008;27(4):328-36
Publication Type
Article
Date
2008
Author
M. Kaare
S. Seitsonen
I. Jarvela
S. Meri
H. Laivuori
Author Affiliation
Folkhälsan Institute of Genetics, University of Helsinki, Finland. milja.kaare@helsinki.fi
Source
Hypertens Pregnancy. 2008;27(4):328-36
Date
2008
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Complement Factor H - genetics
European Continental Ancestry Group
Female
Finland
Gene Frequency
Genotype
Humans
Pre-Eclampsia - genetics
Pregnancy
Retrospective Studies
Abstract
Variations in complement factor H, which down-regulates the activity of the alternative complement pathway, have been associated with different vascular disorders. Here we examine whether factor H variation is involved in the etiology of preeclampsia.
We studied 110 women with preeclampsia and 99 controls for complement factor H variations by sequencing.
No significant differences in the genotype or allele frequencies of the Y402H variant were detected between the two groups. No sequence variations were detected in the short consensus repeat domain 20 of the gene.
Neither the Y402H variant, nor mutations in the short consensus repeat domain 20 of the gene is associated with preeclampsia. For examination of possible links to other polymorphisms or detection of small genotypic effects, studies in larger sample sets are warranted.
PubMed ID
19003634 View in PubMed
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Factor V Leiden as a risk factor for preterm birth--a population-based nested case-control study.

https://arctichealth.org/en/permalink/ahliterature140077
Source
J Thromb Haemost. 2011 Jan;9(1):71-8
Publication Type
Article
Date
Jan-2011
Author
L M Hiltunen
H. Laivuori
A. Rautanen
R. Kaaja
J. Kere
T. Krusius
V. Rasi
M. Paunio
Author Affiliation
Department of Hemostasis, Finnish Red Cross Blood Service, Helsinki, Finland. leena.hiltunen@bts.redcross.fi
Source
J Thromb Haemost. 2011 Jan;9(1):71-8
Date
Jan-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Case-Control Studies
Chi-Square Distribution
Factor V - genetics
Female
Finland
Genetic Predisposition to Disease
Humans
Logistic Models
Middle Aged
Odds Ratio
Polymorphism, Genetic
Pregnancy
Premature Birth - genetics
Prothrombin - genetics
Registries
Risk assessment
Risk factors
Twins - genetics
Venous Thrombosis - genetics
Young Adult
Abstract
Preterm birth is a major cause of neonatal morbidity and mortality, occurring in 5-13% of deliveries in developed countries. Genetic thrombophilia can theoretically contribute to the induction of preterm delivery, but the role of thrombophilia as risk factor is unclear.
To assess factor V Leiden, FII G20210A and other selected inherited and acquired variables as risk factors for preterm birth.
We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Clinical data were obtained from medical records and standardized questionnaires. We studied 324 cases with preterm delivery at or after 22 and before 37 completed weeks of gestation, and 752 controls.
FV Leiden was associated with a 2.4-fold risk (95% confidence interval [CI] 1.3-4.6) of preterm birth in all pregnancies, and a 2.6-fold risk (95% CI 1.4-5.1) in singleton pregnancies. FV Leiden was especially associated with late preterm birth at or after 32 weeks of pregnancy, with an odds ratio (OR) of 2.9 (95% CI 1.5-5.6) in all pregnancies and an OR of 3.1 (95% CI 1.6-6.2) in singleton pregnancies. FII G20210A was not associated with preterm birth. Twin pregnancy (OR 12.0, 95% CI 6.0-24.1) and a history of venous thrombosis (OR 3.8, 95% CI 1.4-9.8) were associated with increased risk. High educational level and modest overweight (body mass index 25-29.9 kg m(-2) ) had protective effects.
Maternal carriage of FV Leiden was associated with increased risk of late but not early preterm birth. FII G20120A was not associated with preterm birth.
PubMed ID
20946152 View in PubMed
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First trimester hyperglycosylated human chorionic gonadotrophin in serum - a marker of early-onset preeclampsia.

https://arctichealth.org/en/permalink/ahliterature107596
Source
Placenta. 2013 Nov;34(11):1059-65
Publication Type
Article
Date
Nov-2013
Author
E. Keikkala
P. Vuorela
H. Laivuori
J. Romppanen
S. Heinonen
U-H Stenman
Author Affiliation
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Biomedicum Helsinki, PB 700, 00029 Helsinki, Finland. Electronic address: elina.keikkala@hus.fi.
Source
Placenta. 2013 Nov;34(11):1059-65
Date
Nov-2013
Language
English
Publication Type
Article
Keywords
Adult
Biological Markers - blood
Case-Control Studies
Chorionic Gonadotropin - blood
Down-Regulation
Female
Fetal Growth Retardation - blood - diagnosis - epidemiology
Finland - epidemiology
Glycosylation
Hospitals, University
Humans
Hypertension, Pregnancy-Induced - blood - diagnosis - epidemiology
Infant, Newborn
Infant, Small for Gestational Age
Male
Maternal Serum Screening Tests
Pre-Eclampsia - blood - diagnosis - epidemiology
Pregnancy
Pregnancy Trimester, First
Pregnancy-Associated Plasma Protein-A - analysis
Principal Component Analysis
Risk factors
Sensitivity and specificity
Young Adult
Abstract
Recent studies indicate that treatment with low-dose aspirin may reduce the risk of preeclampsia. Thus, early prediction of preeclampsia is needed. Low serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) are associated with early pregnancy loss. We therefore studied whether it may serve as an early marker of preeclampsia.
A nested case-control study included 158 women with subsequent preeclampsia, 41 with gestational hypertension, 81 normotensive women giving birth to small-for-gestational-age (SGA) infants and 427 controls participating in first trimester screening for Down's syndrome between 8 and 13 weeks of gestation. Gestational-age-adjusted multiples of medians (MoMs) were calculated for serum concentrations of hCG-h, the free beta subunit of hCG (hCGß) and pregnancy-associated plasma placental protein A (PAPP-A) and the proportion of hCG-h to hCG (%hCG-h). Clinical risk factors including mean arterial pressure (MAP) and parity were also included in the risk calculation.
In women with subsequent preeclampsia %hCG-h was lower than in controls (median MoM 0.92, P
PubMed ID
23993394 View in PubMed
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Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity.

https://arctichealth.org/en/permalink/ahliterature278781
Source
Psychol Med. 2015 Jul;45(10):2023-30
Publication Type
Article
Date
Jul-2015
Author
R M Reynolds
A-K Pesonen
J R O'Reilly
S. Tuovinen
M. Lahti
E. Kajantie
P M Villa
H. Laivuori
E. Hämäläinen
J R Seckl
K. Räikkönen
Source
Psychol Med. 2015 Jul;45(10):2023-30
Date
Jul-2015
Language
English
Publication Type
Article
Keywords
11-beta-Hydroxysteroid Dehydrogenases - analysis
Adult
Depression - physiopathology
Female
Finland
Glucocorticoids - genetics - metabolism
Humans
Linear Models
Placenta - chemistry
Pregnancy
Pregnancy Complications - physiopathology
Pregnancy Trimesters
Psychiatric Status Rating Scales
RNA, Messenger - analysis - genetics - metabolism
Receptors, Mineralocorticoid - analysis
Reverse Transcriptase Polymerase Chain Reaction
Serotonin Plasma Membrane Transport Proteins - analysis - genetics
Young Adult
Abstract
Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.
We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11ß-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies.
In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01-0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01-0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2-3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses).
Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.
PubMed ID
25628053 View in PubMed
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ROCK2 allelic variants are not associated with pre-eclampsia susceptibility in the Finnish population.

https://arctichealth.org/en/permalink/ahliterature151035
Source
Mol Hum Reprod. 2009 Jul;15(7):443-9
Publication Type
Article
Date
Jul-2009
Author
H. Peterson
H. Laivuori
E. Kerkelä
H. Jiao
L. Hiltunen
S. Heino
I. Tiala
S. Knuutila
V. Rasi
J. Kere
K. Kivinen
Author Affiliation
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Source
Mol Hum Reprod. 2009 Jul;15(7):443-9
Date
Jul-2009
Language
English
Publication Type
Article
Keywords
Alleles
European Continental Ancestry Group
Female
Finland
Genetic Predisposition to Disease - genetics
Genotype
Humans
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide - genetics
Pre-Eclampsia - genetics
Pregnancy
Sequence Analysis, DNA
rho-Associated Kinases - genetics
Abstract
The rho-associated coiled-coil protein kinase 2 (ROCK2) gene has been suggested to associate with general hypertension and is therefore a plausible functional candidate gene for pre-eclampsia. ROCK2 maps to chromosome 2p25, which we have implicated previously in a linkage study of pre-eclampsia. We have re-sequenced exons and putative promoter region of ROCK2 in up to 30 pre-eclampsia patients and 22 controls and genotyped putative functional single-nucleotide polymorphisms (SNPs) as well as tagging SNPs from HapMap in a Finnish case-control data set-340 affected and 357 matched control individuals-for a genetic association study of ROCK2 in pre-eclampsia. Even though several new SNPs were discovered, we did not detect significant allelic or haplotypic association between ROCK2 and pre-eclampsia. We assessed ROCK2 expression in placentas by microarray analysis, but no significant expression differences were observed when comparing preeclamptic and normotensive pregnancies. We conclude that common genetic variation in ROCK2 is unlikely to make a major contribution to the risk of pre-eclampsia, but cannot exclude the possibility of having missed non-coding functional variants or rare coding variants.
PubMed ID
19435756 View in PubMed
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8 records – page 1 of 1.