OBJECTIVES: To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). METHODS: Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. RESULTS: Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). CONCLUSIONS The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.
Female ; Pregnancy ; Infant, Newborn ; Humans ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics* ; Pre-Eclampsia/genetics* ; Gene Frequency ; Genotype ; Polymorphism, Single Nucleotide ; Alleles

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 1 (VEGFR1) pathways-related genes and the risk of pre-eclampsia. METHODS: In total 178 pregnant women with pre-eclampsia (case group) and 100 healthy pregnant women (control group) during the third trimester were enrolled. The SNPs of VEGF rs3025039, rs2010963 and VEGFR1 rs3812867, rs55875014 and rs722503 loci were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The levels of serum VEGF and sVEGFR1 were also determined. And their association with pre-eclampsia was analyzed. RESULTS: The systolic blood pressure, diastolic blood pressure and sVEGFR1 of the case group were significantly higher than those of the control group, while the VEGF level was significantly lower than that in the control group (P<0.05). Allelic frequencies of the VEGF (rs3025039, rs2010963) and VEGFR1 (rs3812867, rs55875014, rs722503) have fit the Hardy-Weinberg equilibrium (P>0.05). The frequency of T allele of VEGF at rs3025039 locus in the case group was higher than that in the control group (P<0.05). There were significant differences in VEGF at rs3025039 locus under dominant and co-dominant models in case group (P<0.05). Compared with those with CC, the risk was higher in patients with CT or TT genotypes (P<0.05). The systolic and diastolic blood pressure and sVEGFR1 in pre-eclampsia pregnant women with CT or TT genotypes were significantly higher than those with the CC genotype, while their VEGF level was significantly lower (P<0.05). No significant difference was found in allelic frequencies of other four loci between the two groups (P>0.05). CONCLUSION Polymorphisms of rs3025039 locus of VEGF gene is associated with the occurrence of pre-eclampsia. The variant at this locus may affect the activity of VEGF and influence the development of pre-eclampsia.
Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Pre-Eclampsia/genetics* ; Pregnancy ; Vascular Endothelial Growth Factor A/genetics* ; Vascular Endothelial Growth Factor Receptor-1/genetics* ; Vascular Endothelial Growth Factors/genetics*

OBJECTIVE: To investigate the effects of ALKBH5 on migration, invasion and epithelial-mesenchymal transition (EMT) of human trophoblast cells. METHODS: The expression plasmid of ALKBH5 or a negative control plasmid (ALKBH5-NC) was transfected in human trophoblast HTR-8 /SVneo cells, and the expressions of ALKBH5 mRNA and protein were detected by qRT-PCR and Western blotting. Transwell assay was used to assess the changes in migration and invasion abilities of the trophoblast cells after the transfection. Western blotting was performed to detect the expressions of EMT-related proteins in the cells including vimentin, fibronectin, E-cadherin, N-cadherin, MMP9 and MMP2. RESULTS: ALKBH5 mRNA and protein expressions were significantly higher in ALKBH5 group than in the control group ( CONCLUSIONS ALKBH5 is involved in the pathogenesis of preeclampsia by inhibiting EMT of trophoblast cells and hence reducing their migration and invasion abilities.
AlkB Homolog 5, RNA Demethylase ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Pre-Eclampsia ; Pregnancy ; Trophoblasts ; Vimentin/genetics*

OBJECTIVE: To investigate the effect of vitamin D on microRNA-21(miR-21) expression and migration and invasion of human placental trophoblast cells. METHODS: The changes in the expression of miR-21 were detected using RT-qPCR in HTR-8/SVneo cells following stimulation by vitamin D at different doses for 24, 48 and 72 h.HTR-8/SVneo cells transfected with miR-21 mimic or inhibitor with or without vitamin D treatment were examined for changes in cell migration and invasion abilities using Transwell assay, and Western blotting was used to detect protein expressions of E-cadherin, fibronectin, and MMP9. RESULTS: Vitamin D obviously inhibited the expression of micoRNA-21 in HTR-8/SVneo cells in a concentration-and time-dependent manner.Transfection with the miR-21 mimic significantly inhibited the migration and invasion of HTR-8/SVneo cells, and this inhibitory effect was abolished by treatment with vitamin D; transfection with miR-21 inhibitor obviously promoted the migration and invasion of HTR-8/SVneo cells, and these effects were not significantly affected by vitamin D treatment. CONCLUSIONS Vitamin D may promote trophoblast cell migration and invasion to accelerate the development of preeclampsia by down-regulating the expression of miR-21.
Cell Movement ; Female ; Humans ; MicroRNAs ; genetics ; Placenta ; Pre-Eclampsia ; Pregnancy ; Trophoblasts ; Vitamin D

OBJECTIVETo assess the association of IFNG gene polymorphisms with preeclampsia among pregnant woman from Shaanxi Province.

METHODSGenomic DNA was extracted from peripheral blood samples collected from 280 patients with preeclampsia and 344 healthy pregnant women. Five tag single nucleotide polymorphisms (SNPs) of the IFNG gene (rs2069705, rs2430561, rs1861493, rs2069718, and rs2193050) were genotyped with a SNaPshot method. Genotypic and allelic frequencies were evaluated with a Chi square test. Genotype data was corrected by Logistic regression for body mass index and age. The level of IFN-gamma was determined with an ELISA assay.

RESULTSThe distribution of five tag SNPs all conformed to Hardy-Weinberg equilibrium (P> 0.05). Significant association with preeclampsia was found with the T allele of rs2430561 (OR=1.54, 95% CI:1.15-2.09, P=6.99× 10), under a dominant model (OR=3.77, 95% CI: 1.09-13.29, P=0.029) and a recessive model (OR=1.53, 95% CI:1.09-2.15, P=0.018). For the patient group, the IFN-gamma level of those with a TT genotype for rs2430561 was significantly higher than those with an AA or AT genotype [(13.69± 0.79) pg/mL vs. (13.11± 1.56) pg/mL, P< 0.05].

CONCLUSIONPolymorphism of the rs2430561 locus of the IFNG gene is associated with increased risk for preeclampsia as well as serum level of IFN-gamma among pregnant woman from Shaanxi. The role of the IFNG gene in the regulation of preeclampsia requires further investigation.

Adult ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interferon-gamma ; blood ; genetics ; Logistic Models ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; etiology ; genetics ; Pregnancy

OBJECTIVETo investigate the relationship between polymorphisms of the growth arrest specific 6 (GAS6) gene and severe preeclampsia in a South West Han Chinese population.

METHODSBlood samples from 167 patients with severe preeclampsia and 312 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms.

RESULTSC and T allele frequencies for +1332C/T site were 85.63% and 14.37% in the patient group, respectively, and 78.04% and 21.96% in control group, respectively. The TT genotype and variant T allelic frequencies of the +1332C/T polymorphism were significantly lower in patients with severe preeclampsia than in the control group (both P<0.05), and the odds ratio for the risk of severe preeclampsia was 0.602 (95%CI: 0.401-0.904) in carriers for the variant T allele (χ=6.045, P=0.014). G and A allele frequencies for 834+7G/A site were 72.75% and 27.25% in case group, respectively, and 74.36% and 25.64% in control group, respectively. The genotype and allele frequencies of the 834+7G/A polymorphism in patients with severe preeclampsia and controls showed no significant differences (both P>0.05). In addition, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups.

CONCLUSIONThe variant GAS6+1332 T allele is associated with a decreased risk for severe preeclampsia in a South West Han Chinese population. On the other hand, the 834+7G/A polymorphism has no effect on the severe preeclampsia.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; ethnology ; genetics ; pathology ; Pregnancy ; Risk Factors ; Severity of Illness Index ; Young Adult

Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively. Results showed the expression levels of Axl mRNA and protein were significantly higher in both placentas and EPCs from preeclampsia patients than from normal pregnancy (P<0.05). After treatment with BMS777-607, proliferation, differentiation, migration and adhesion capability of EPCs were all significantly decreased. Our study suggests Axl may play a role in the function of EPCs, thereby involving in the pathogenesis of preeclampsia.
Adult ; Aminopyridines ; pharmacology ; Blood Pressure ; Case-Control Studies ; Cell Adhesion ; drug effects ; Cell Differentiation ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Female ; Fetal Blood ; cytology ; enzymology ; Gene Expression Regulation ; Gestational Age ; Human Umbilical Vein Endothelial Cells ; drug effects ; enzymology ; pathology ; Humans ; Placenta ; metabolism ; physiopathology ; Pre-Eclampsia ; blood ; genetics ; physiopathology ; Pregnancy ; Primary Cell Culture ; Protein Kinase Inhibitors ; pharmacology ; Proto-Oncogene Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Pyridones ; pharmacology ; RNA, Messenger ; antagonists & inhibitors ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; genetics ; metabolism ; Stem Cells ; drug effects ; enzymology ; pathology

OBJECTIVETo assess the association of prostasin gene rs12597511 polymorphism with clinical features and pregnancy outcomes among patients with severe preeclampsia.

METHODSClinical manifestations, pregnancy outcomes and the genotypes of 179 patients with severe preeclampsia [early-onset group (≤34 gestational weeks): 79 cases; Late-onset group (>34 gestational weeks): 100 cases] and 222 normal-term pregnant women (control group) were collected.

RESULTSIn the early-onset group, the patients with TC or CC genotype at rs12597511 had higher incidences of total complications, liver dysfunction, neonatal asphyxia, neonatal intracranial hemorrhage and perinatal mortality compared with those with TT genotype (P>0.05). Multiple logistic regression analysis showed that the complication rates of severe preeclampsia patients are closely related to TC or CC genotypes, 24 h urinary protein and gestational weeks of onset (OR=1.049, 95% CI:1.007-1.093, P=0.021; OR=1.031, 95% CI: 0.350-0.883, P=0.013; OR=0.733, 95% CI: 0.566-0.950, P=0.019), and the perinatal mortality is related to gestational weeks at delivery (OR=0.542, 95% CI: 0.331-0.887, P=0.015).

CONCLUSIONPolymorphism of the prostasin gene is closely associated with poor pregnancy outcomes of early-onset severe preeclampsia.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Male ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; enzymology ; genetics ; physiopathology ; Pregnancy ; Pregnancy Outcome ; Serine Endopeptidases ; genetics

OBJECTIVETo detect changes of Foxp3 expression in the decidua in patients with preeclampsia and investigate the correlation of Foxp3-924 (rs2232365) polymorphisms with preeclampsia.

METHODSFrom October 2011 to December 2012, 252 normal pregnant women and 156 preeclampsia patients of Han nationality from the same geographic region were tested for Foxp3-924 genotypes by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sixty-eight of the patients with preeclampsia (33 with mild and 35 with severe preeclampsia) and 30 of the normal pregnant women were also examined for Foxp3 expression in the decidua using immunohistochemical method.

RESULTSFoxp3 positive expression rates in the decidua was 51.52% in mild preeclampsia and 28.57% in severe preeclampsia cases, significantly lower than that in the control group (86.67%, P<0.05). In preeclampsia patients, the frequencies of Foxp3-924G/G, G/A, and A/A genotypes were 0.1346, 0.4615 and 0.4038, respectively, and the frequencies of Foxp3-924A and Foxp3-924 G were 0.6346 and 0.3654, respectively. The genotype frequencies of Foxp3-924G/G, G/A and A/A in the control group were 0.1508, 0.4087 and 0.4405, respectively, and the frequencies of Foxp3-924 A and Foxp3-924 G were 0.6448 and 0.3552, respectively. No significant differences were found in the gene frequencies of Foxp3-924G/A between preeclampsia patients and the control group (P>0.05).

CONCLUSIONThe expression level of Foxp3 in the placental tissue of preeclampsia patients is significantly lower than that in normal pregnant women, suggesting that lowered Foxp3 expression decreases the immunosuppressive function and causes imbalance of immune tolerance between maternal-fetal to induce preeclampsia. Foxp3-924 polymorphisms is not significantly correlated with the occurrence of preeclampsia.

Case-Control Studies ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Frequency ; Genotype ; Humans ; Placenta ; metabolism ; Polymorphism, Genetic ; Pre-Eclampsia ; genetics ; Pregnancy

OBJECTIVETo investigate the relationship between two polymorphisms immediately upstream of the cyclooxygenase 2 (COX2) gene and preeclampsia in a South West Han Chinese population.

METHODSBlood samples from 205 patients with preeclampsia and 276 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms.

RESULTSG and A allele frequencies for -1195G>A site were 48.54% and 51.46% in the patient group, respectively, and 40.40% and 59.60% in the control group, respectively. G and C allele frequencies for -765G>C site were 94.15% and 5.85% in the case group, respectively, and 94.38% and 5.62% in the control group, respectively. The AA genotype and variant A allelic frequencies of the -1195G>A SNP were significantly lower in patients with preeclampsia than in the control group (P<0.05), and the odds ratio for the risk of preeclampsia was 0.665 (95% CI: 0.444-0.982) in women homozygous for the variant COX2 A allele ( x²=4.233, P=0.047). The genotype and allele frequencies of the -765G>C polymorphism in patients with preeclampsia and controls showed no significant differences (P>0.05). Additional subgroup analyses (mild vs severe preeclampsia) of the two polymorphisms failed to reveal significant correlation for either genotypic or allelic frequencies. Furthermore, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups.

CONCLUSIONCOX2 -1195A homozygosity is associated with a decreased risk for preeclampsia in a South West Han Chinese population. On the other hand, the -765G>C polymorphism has no effect.

Adult ; Alleles ; Blood Pressure ; Case-Control Studies ; China ; Cyclooxygenase 2 ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; enzymology ; genetics ; physiopathology ; Pregnancy ; Risk Factors