osteoprotegerin and Pre-Eclampsia

Pre-eclampsia is a known risk factor for long-term cardiovascular complications. Osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) have been implicated in the pathogenesis of cardiovascular disease. The OPG-RANKL axis function is also altered in pregnant women with pre-eclampsia, but there is lack of data regarding OPG and RANKL concentrations in their neonates.. To examine the effects of early-onset pre-eclampsia on OPG and RANKL serum concentrations at birth, taking into account the influence of various perinatal factors.. OPG and RANKL serum concentrations were measured in 28 premature newborns of mothers with early onset pre-eclampsia, and in 28 preterm and 28 full-term neonates of normotensive mothers (control groups).. Neonates of pre-eclamptic mothers had higher OPG and lower RANKL levels compared to both control groups (Kruskal-Wallis P < 0.0001 and P = 0.014, respectively). Regression analysis showed that pre-eclampsia (P < 0.0001), birth weight z-score (P = 0.048) and antenatal steroid administration (P = 0.034) were significant determinants of OPG levels. Multivariable regression analysis also showed that pre-eclampsia was an independent predictor of increased diastolic and mean blood pressure in these neonates.. Early-onset pre-eclampsia affects OPG concentrations at birth and is an independent predictor of increased blood pressure in the offspring. Our findings suggest that altered OPG-RANKL axis function may be one of the mechanisms of cardiovascular 'programming' in fetuses exposed to pre-eclampsia.

Topics: Adult; Biomarkers; Blood Pressure; Female; Humans; Hypertension; Infant, Newborn; Male; Osteoprotegerin; Pre-Eclampsia; Pregnancy; Prenatal Exposure Delayed Effects; RANK Ligand

The aim of this study was to detect the role of osteoprotegerin (OPG) gene variants in early-onset severe pre-eclampsia.. The associations of 163A/G (rs3102735) and 950T/C (rs2073617) polymorphisms of OPG with pre-eclampsia (60 cases of early-onset severe pre-eclampsia and 91 cases of late-onset pre-eclampsia), as well as with the clinical manifestations of individuals, were evaluated.. Data showed lower frequencies of TC and TC + CC genotypes and C allele of 950T/C in the early-onset group than those of the control and late-onset groups (P = 0.003; P = 0.002; P = 0.005; P = 0.031; P = 0.021; P = 0.022). However, no significant differences were found in genotype and allele frequencies between the late-onset and control groups. Moreover, no significant differences were observed in the genotype and allele frequencies of 163A/G polymorphism among the three groups. In the early-onset group, 950T/C TC + CC genotype carriers exhibited significantly lower systolic blood pressure ([147.25 ± 11.89] mmHg) and 24-h urine protein ([2.46 ± 0.92] g) than the TT carriers ([165.88 ± 20.39] mmHg, [3.64 ± 0.81] g) (P = 0.003; P = 0.001, respectively). Serum creatinine was significantly higher in women with the 163A/G AG + GG genotypes ([82.31 ± 11.66] μmol/L) than in those with the AA genotype ([71.90 ± 16.85] μmol/L) (P = 0.003).. This study implicates that OPG gene variants may be associated with early-onset severe pre-eclampsia.

Topics: Adult; Female; Gene Frequency; Genotype; Humans; Osteoprotegerin; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Severity of Illness Index; Time Factors; Young Adult

The purpose of our study was to investigate the concentrations of markers of bone turnover in normal pregnancy and preeclampsia.. Forty-five pregnant patients with preeclampsia, 78 healthy pregnant women (26 in first, 26 in the second, and 26 in third trimester of pregnancy), and 20 nonpregnant women were included in the study. Serum concentrations of osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps-degradation products of type I collagen, were determined using the ELISA method. Statistical analysis was performed using Mann-Whitney U-test.. The concentrations of sRANKL and OPG were significantly higher in the second trimester of normal pregnancy when compared to the first and the third trimesters and to nonpregnant controls. The concentrations of osteocalcin were significantly higher in the first trimester of physiological pregnancy in comparison with nonpregnant women and with second and third trimesters of pregnancy. The concentrations of CrossLaps were significantly higher in the second trimester of normal pregnancy when compared to the first and third trimester. In preeclampsia, the sera concentrations of osteocalcin and CrossLaps were significantly higher when compared to the third trimester of normal pregnancy.. The results suggest that the bone formation is increased in the first trimester, whereas the bone resorption is increased in the second trimester of normal pregnancy. Furthermore, the results suggest that the bone turnover is increased in patients with preeclampsia when compared to healthy normotensive pregnant women.

Topics: Adult; Biomarkers; Bone and Bones; Case-Control Studies; Collagen; Female; Humans; Osteocalcin; Osteoprotegerin; Peptide Fragments; Pre-Eclampsia; Pregnancy; RANK Ligand; Young Adult

To investigate the potential association between 163A/G and 950T/C polymorphisms of osteoprotegerin (OPG) gene and severe pre-eclampsia.. Eighty-five severe pre-eclamptic patients and 81 normal term pregnant women (as control group) were recruited from the Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University during the period from July 2007 to March 2009, and they were all Han population living in Chengdu, China. Genotype and allele frequencies of 163A/G and 950T/C were determined by the PCR-restriction fragment length polymorphism (RFLP) assay. Clinical and biochemical parameters for different alleles between the patients and controls were compared for statistical significance respectively, such as blood pressure, serum creatinine and 24-hour urine protein.. The observed and expected genotype counts were consistent with Hardy-Weinberg equilibrium. No significant differences were found in the genotype and allele frequencies of 163A/G and 950T/C polymorphisms between the two groups (P > 0.05). However, in the preeclamptic group, serum creatinine was significantly higher in women with the AG + GG genotypes [(76 ± 24) µmol/L] compared with AA genotype [(56 ± 18) µmol/L]. Reversely, birth weight was lower in the AG + GG genotypes [(2040 ± 721) g] than those in the AA genotype [(2520 ± 810) g], and the P < 0.05, respectively. In the severe pre-eclampsia, 950T/C TT genotype carriers exhibited significantly higher systolic blood pressure [(153 ± 16) mm Hg (1 mm Hg = 0.133 kPa)] and 24-hour urine protein [(4.0 ± 2.5) g] compared with TT + TC carriers [(145 ± 17) mm Hg, (2.9 ± 1.8) g], respectively, furthermore the P < 0.05.. In severe pre-eclampsia, carriers with G allele at position 163A/G has more genetic predisposition than A allele carriers, as well as 950T/C T allele carriers compared with C carriers. Taken together, this study suggested that OPG gene polymorphisms might be associated with some clinical parameters of severe pre-eclampsia.

Topics: Adult; Alleles; Asian People; Birth Weight; Blood Pressure; Case-Control Studies; China; Creatinine; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Osteoprotegerin; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Risk Factors; Severity of Illness Index

Osteoprotegerin (OPG), a key regulatory factor in bone metabolism, was documented also a potential pro-angiogenic factor, which acts an important role in protecting vascular endothelial cells. Since preeclampsia has gradually been employed to be vascular diseases, we speculated that OPG might be associated with preeclampsia. The study was to evaluate the level of OPG protein and mRNA in placenta, and investigate the relationship between OPG and the pathogenesis of preeclampsia.. Placental specimens from 30 term normal pregnancy, 30 severe preeclampsia and 30 mild cases were studied. The expression and levels of OPGs' protein and mRNA were detected by immunohistochemistry, western blot analysis and real-time quantitative PCR analysis respectively. The expression of OPG protein was found in cytoplasm of placenta cytotrophoblasts and syncytiotrophoblasts in three groups. There were no significant differences of OPG protein between the maternal and fetal side in each group. The OPG protein and mRNA levels in severe preeclampsia were significantly higher than those in mild cases and normal pregnancy. However, there were no markedly differences of the OPG protein and mRNA levels between term delivery and preterm delivery in severe cases. In preeclampsia, the OPG protein and mRNA level was positively correlated with systolic blood pressure and 24 h urinary protein respectively.. OPG protein and mRNA level in placentas of preeclampsia were found abnormal compared with normal pregnancy. In preeclampsia, the OPG protein and mRNA levels were closely related with its important clinical parameters. Taken together, OPG might be closely correlated with the pathogenesis of preeclampsia.

Topics: Adult; Blotting, Western; Demography; Female; Gene Expression Regulation; Humans; Osteoprotegerin; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger

To evaluate alterations in the concentrations of osteoprotegerin (OPG), RANKL and the OPG/RANKL ratio in pre-eclamptic women during the puerperium.. This cross-sectional study was performed in the maternity ward of Aretaieio Hospital in Athens, Greece. Fifteen pregnant women with severe pre-eclampsia and 15 matched controls with premature rupture of the membranes were recruited. Fasting blood samples were obtained antepartum, immediately after diagnosing pre-eclampsia (median: 32nd gestational week), and during the 3rd-6th day postpartum, to estimate levels of circulating OPG and RANKL as well as the OPG/RANKL ratio. The anthropometric parameters evaluated included body mass index and blood pressure.. Mean circulating OPG levels decreased significantly in both groups in the postpartum period (controls: 43.7 ± 19.1 ng/ml vs 22.9 ± 9.1 ng/ml, p = 0.008; pre-eclamptic group: 72.3 ± 49.9 vs 49.7 ± 40.9 ng/ml, p = 0.002). The antepartum OPG/RANKL ratio was elevated in hypertensive pregnancies (2.41 ± 1.72) compared to normotensive pregnancies (1.45 ± 0.63), but the difference did not reach statistical significance (p = 0.1). The OPG/RANKL ratio decreased in the control group (0.76 ± 0.30, NS) following delivery, while it remained unchanged in the pre-eclamptic women (1.63 ± 1.40, p = 0.13). Consequently, the postpartum OPG/RANKL ratio was significantly higher in the pre-eclamptic women compared to control women (1.63 ± 1.40 vs 0.76 ± 0.30, p = 0.01). Levels of RANKL demonstrated no significant alterations during puerperium in both cases.. Pregnancies complicated with pre-eclampsia exhibit higher OPG levels and OPG/RANKL ratios, compared to control pregnancies, which might be compatible with lower bone turnover. The significance of this finding with respect to bone metabolism remains to be elucidated in larger studies.

Topics: Adult; Bone and Bones; Cross-Sectional Studies; Female; Fetal Membranes, Premature Rupture; Humans; Osteoprotegerin; Pre-Eclampsia; Pregnancy; RANK Ligand