We determined whether the polymorphism of the gene encoding adiponectin contributes to susceptibility to preeclampsia. The study involved 133 Finnish women with preeclampsia and 245 healthy control subjects. All women were genotyped for two single nucleotide polymorphisms (SNPs), SNP45 in exon 2 and SNP276 in intron 2, in the adiponectin gene. Chi2 analysis was used to assess genotype and allele frequency differences between the preeclamptic and control groups. In addition, the pair of loci haplotype analysis, using the expectation-maximization (EM) algorithm, was used to examine the estimated haplotype frequencies of the two SNPs, among the two groups. The TT genotype versus the pooled G genotypes in SNP276 was associated with protection against preeclampsia (p = 0.012) at an odds ratio of 0.27 (95% confidence interval [CI]: 0.09-0.80). Also the genotype and allele frequency distributions of SNP276 differed significantly between the preeclampsia group and the control group (p = 0.035 and p = 0.043, respectively). Single-point genotype and allele distributions in SNP45 of the adiponectin gene were not statistically different between the groups. In the haplotype estimation analysis, the pooled G haplotypes versus the TT haplotype were significantly overrepresented in the preeclampsia group (p = 0.042 +/- 0.005). Polymorphisms of the adiponectin gene show a weak, but statistically significant, haplotype association with susceptibility to preeclampsia in Finnish women.
The aim of this study was to evaluate changes in the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) levels during different menstrual cycle phases in young adult women with or without oral contraceptive (OC) use.
The subjects (n=1079) originated from a large population-based, prospective cohort study conducted in Finland. Plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, C-reactive protein, creatinine, and brachial artery flow-mediated dilatation (FMD) were measured. The use of OCs and menstrual cycle phase were determined from a questionnaire.
In non-OC users, ADMA (P=0.017), L-arginine (P=0.002), and ADMA/SDMA ratio (P
Anaemia during pregnancy is an important public health problem. We investigated whether the association between maternal anaemia during pregnancy and adverse perinatal outcomes differed between nulliparous and multiparous women.
A retrospective population-based cohort study was conducted using data on all singleton births (n?=?290?662) recorded in the Finnish Medical Birth Register during 2006-10. Maternal anaemia was defined as a maternal haemoglobin level of
To assess pregnancy outcome in women with anaemia during pregnancy.
The study design involved a retrospective chart review of all women registering for prenatal care in the area of Kuopio University Hospital between 1990 and 2000. A haemoglobin concentration below 100g/l was used as a cutoff for anaemia and affected women (N=597) were stratified by the trimester at which anaemia was diagnosed. Multiple regression analysis was used to compare obstetric outcomes in the study groups and in non-anaemic women (N=22,202).
The frequency of anaemia was 2.6%, with 0.3% occurring in the first trimester. After controlling for confounding factors, anaemia detected in the first trimester was associated with low-birth-weight infants (OR=3.14, 95% CI: 1.35-7.28) whereas the mid- and third-trimester anaemia groups showed no significantly different outcomes when compared with the non-anaemic women. First trimester anaemia was not significantly associated with small birth weight for gestational age (OR=0.98, 95% CI: 0.41-2.17) or with premature delivery
The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke.
First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women.
PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6-48.5) pg/ml, p?=?.001] and reduced sEng concentration [5.0 (4.6-5.6) ng/ml, p?=?.047] compared to PE non-smokers [30.0 (28.1-32.1) pg/ml and 6.1 (5.9-6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy.
The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker. Key messages Smoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies. Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.
To study first and second/third trimester levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in FINNPEC case-control cohort. The participants were further divided into subgroups based on parity and onset of the disease. Recommended cut-off values in aid of pre-eclampsia (PE) prediction and diagnosis were also tested.
First trimester serum samples were available from 221 women who later developed PE and 239 women who did not develop PE. Second/third trimester serum samples were available from 175 PE and 55 non-PE women. sFlt-1 and PlGF were measured electro-chemiluminescence immunoassays and sEng by ELISA.
In all timepoints PlGF, endoglin and the sFlt-1/PlGF ratio were increased in the PE group compared to the non-PE group. The serum concentrations of sFlt-1 were increased only at second/third trimester in PE women. Higher concentrations of s-Flt1, endoglin and higher sFlt/PlGF ratio were found at the third trimester in primiparous women compared to multiparous women. Primiparous PE women also had lower concentrations of PlGF at the third trimester. The proportion of women exceeding all cut-offs of the sFlt-1/PlGF ratio (=33, =38, =85 and?=110) was greater in the PE group, but there were also pre-eclamptic women who met rule-out cut-off or did not meet rule-in cut-off.
Primiparous pregnancies have more anti-angiogenic profile during second/third trimester compared with multiparous pregnancies. Our findings also suggest that certain maternal characteristics, e.g. BMI, smoking and pre-existing diseases, should be taken into account when different sFlt-1/PlGF ratio cut-offs are utilized.
The aim of this study was to investigate the association of risk variants for type 2 diabetes (T2D) and hyperglycemia with gestational diabetes (GDM).
Five hundred and thirty-three Finnish women who were diagnosed with GDM and 407 controls with normal glucose tolerance during the pregnancy were genotyped for 69 single-nucleotide polymorphisms (SNPs) which have been previously verified as susceptibility risk variants for T2D and hyperglycemia. All participants underwent an oral glucose tolerance test at the follow-up study after the index pregnancy.
Risk variants rs10830963 and rs1387153 of MTNR1B were significantly associated with GDM (odds ratio (OR)=1.62 (95% CI 1.34-1.96), P=4.5 × 10?7 and 1.38 (1.14-1.66), P=7.6 × 10?4 respectively). Both SNPs of MTNR1B were also significantly associated with elevated fasting glucose level and reduced insulin secretion at follow-up. Additionally, risk variants rs9939609 of FTO, rs2796441 of TLE1, rs560887 of G6PC2, rs780094 of GCKR, rs7903146 of TCF7L2 and rs11708067 of ADCY5 showed nominally significant associations with GDM (OR range from 1.25 to 1.30).
Our study suggests that GDM and T2D share a similar genetic background. Our findings also provide further evidence that risk variants of MTNR1B are associated with GDM by increasing fasting plasma glucose and decreasing insulin secretion.
In the present study we determined whether genetic variability in the gene encoding adiponectin is associated with polycystic ovary syndrome (PCOS). Altogether 143 Caucasian women with PCOS and 245 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) in exon 2 and intron 2 in the adiponectin gene. Single-point analysis was expanded to pair-of-loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization algorithm. A significantly different allele distribution in intron 2 SNP was observed between the groups, with the T allele being significantly reduced in the PCOS group (25.9%) compared with the control group (32.7%) ( p = 0.047), at an odds ratio of 0.72 (95% confidence interval 0.52-0.99). Otherwise, the allele and genotype distributions in either SNP were not statistically different between the groups. In haplotype estimation analysis, there was a lower frequency of the haplotype T-T in the PCOS group (25.9%) than in the control group (32.7%) ( p = 0.058). We conclude that polymorphisms of the adiponectin gene may be implicated in individual susceptibility to PCOS.
Mutations in the BRCA1/2 genes confer a high risk for breast and ovarian cancer, with usually adverse clinical characteristics. The clinical course and response to treatment in mutation carriers have been reported infrequently and are assumed to be worse than in sporadic breast cancer.
Eleven members of an Eastern Finnish family with multiple cases of breast and ovarian cancers were screened for BRCA1/2 mutations using protein truncation test (PTT), conformation-sensitive gel electrophoresis (CSGE) and sequencing.
Five of the six BRCA2 4088insA mutation carriers were affected. Mutation-positive breast/ovarian cancer patients had an excellent response to treatment even when prognosis as assessed by classical factors was poor.
The 4088insA mutation appears to be associated with a favourable clinical course of breast and ovarian cancer, providing an informative example on the role of an individual mutation in assessing the prognosis for mutation carriers. Our results encourage more research on the effects of an individual mutation on clinical characteristics, response to treatment and outcome.
To evaluate the association between gestational age at birth and the risk of subsequent development of asthma.
We conducted a retrospective observational hospital-based birth case-control study in a university-based obstetrics and gynecology department in Finland. A total of 44,173 women delivering between 1989 and 2008 were linked with the social insurance register to identify asthma reimbursements for their offspring (n = 2661). Pregnancy factors were recorded during pregnancy. Infants were categorized as moderately preterm (= 32 weeks), late preterm (33-36 weeks), early term (37-38 weeks), term (39-40 weeks), or late term and postterm (= 41 weeks). The main outcome measure was asthma among the infants.
Children born moderately preterm (= 32 weeks gestation) had a significantly increased risk of asthma (aOR, 3.9; 95% CI, 3.2-4.8). The risk of asthma was also increased in those born late preterm (aOR, 1.7; 95% CI, 1.4-2.0) and early term (aOR, 1.2; 95% CI, 1.1-1.4). In contrast, delivery at 41 weeks or later seemed to decrease the risk of asthma (aOR, 0.9; 95% CI, 0.8-1.0). The burden of asthma associated with preterm birth was associated mainly with early term infants, in whom 108 extra cases of asthma were observed.
Even though the individual risk of asthma was inversely correlated with gestational age at birth, the overall burden brought about by delivery before term was associated with late preterm and early term deliveries. Furthermore, delivery after term was protective against asthma.