Xinghui Liu

Association Between Val158Met Functional Polymorphism in the COMT Gene and Risk of Preeclampsia in a Chinese Population

BACKGROUND AND AIMS The catechol-O-methyltransferase (COMT) gene is a potential candidate in altering risk for preeclampsia due to the important enzymatic effects in the metabolism of steroid hormones. It contains a non-synonymous G-A base change at codon 158 in the membrane bound isoform, which leads to a valine-to-methionine amino acid substitution. In the soluble isoform the polymorphism rs4680 is located in codon 108. The variant allele is the Met (A) allele and the Val (G) allele is the wild type allele. Despite its previously reported association with preeclampsia in genotypes in three selected ethnic groups, further studies in other populations are required. METHODS We genotyped the Val158Met polymorphism in the COMT gene by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis in a Chinese population. RESULTS In the case-control study that included 187 patients with preeclampsia (cases) and 189 normal subjects (controls), the AA genotype and variant Met allele frequencies of Val158Met in the COMT gene were significantly higher in patients with preeclampsia than those in the control group (both p <0.05). The odds ratio for the risk of preeclampsia was 2.395 [95% confidence interval (CI): 1.061-5.408] in women homozygous for the variant COMT allele (χ(2) = 4.649, p = 0.031). Furthermore, it showed that obese women homozygous for the variant COMT allele (Met/Met) had higher diastolic blood pressure levels during pregnancy than wild-type homozygotes (Val/Val) (p = 0.034). CONCLUSIONS Our study provided evidence in favor of COMT being a candidate gene for conferring genetic susceptibility to preeclampsia in a South West Chinese population.

A Small Physiological Electric Field Mediated Responses of Extravillous Trophoblasts Derived from HTR8/SVneo Cells: Involvement of Activation of Focal Adhesion Kinase Signaling

Moderate invasion of trophoblast cells into endometrium is essential for the placental development and normal pregnancy. Electric field (EF)-induced effects on cellular behaviors have been observed in many cell types. This study was to investigate the effect of physiological direct current EF (dc EF) on cellular responses such as elongation, orientation and motility of trophoblast cells. Immortalized first trimester extravillous trophoblast cells (HTR-8/SVneo) were exposed to the dc EF at physiological magnitude. Cell images were recorded and analyzed by image analyzer. Cell lysates were used to detect protein expression by Western blot. Cultured in the dc EFs the cells showed elongation, orientation and enhanced migration rate compared with non-EF stimulated cells at field strengths of 100 mV/mm to 200 mV/mm. EF exposure increased focal adhesion kinase (FAK) phosphorylation in a time-dependent manner and increased expression levels of MMP-2. Pharmacological inhibition of FAK impaired the EF-induced responses including motility and abrogated the elevation of MMP-2 expression. However, the expression levels of integrins like integrin α1, α5, αV and β1 were not affected by EF stimulation. Our results demonstrate the importance of FAK activation in migration/motility of trophobalst cells driven by EFs. In addition, it raises the feasibility of using applied EFs to promote placentation through effects on trophoblast cells.

Genotype distribution of estrogen receptor α polymorphisms in pregnant women from healthy and preeclampsia populations and its relation to blood pressure levels

Abstract Background: The estrogen receptor α gene (ESR1) seems to be a potential candidate in altering risk for preeclampsia due to important estrogenic biological effects. Despite its previously reported association with severe preeclampsia in combined genotype in one selected ethnic group, further studies in other populations are required. The objective of this study was to investigate the relationship of the gene polymorphisms of the estrogen receptor α with preeclampsia in a southwest Chinese population. Methods: We genotyped two polymorphisms in the ESR1 gene (PvuII and XbaI) by polymerase chain reaction-restriction fragment length polymorphism analysis in a Chinese population. Results: In the case-control study which included 204 preeclampsia case subjects and 236 normal control subjects, the frequencies of allele T for the PvuII site and allele G for the XbaI site in the patients (41.67% and 23.53%, respectively) were similar to those observed in controls (43.01% and 19.70%, respectively). Furthermore, the combined genotype analysis of ESR1 PvuII and XbaI polymorphisms showed no increased risk of either severe or total preeclampsia in our study populations. However, it showed that the CC homozygotes and CT heterozygotes in control pregnant women had higher systolic blood pressure levels than TT homozygotes for the PvuII site after adjustment for age and body mass index (p<0.05). Conclusions: Our work does not provide evidence in favor of ESR1 PvuII and XbaI being associated with preeclampsia but with increased blood pressure levels in normal pregnant women, in a southwest Chinese population. Clin Chem Lab Med 2009;47:391–7.

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

Objectives: The objective of the study was to investigate the relationship of a C825T polymorphism of the gene encoding the G protein β3 subunit with preeclampsia in a South-West Chinese population. Results: In the case-control study which included 221 preeclamptic case subjects and 277 normal control subjects the allele frequency of 825C→T in the GNB3 gene was 47.29% in patients with preeclampsia and 49.28% in the control group. Furthermore, there was no significant association between the polymorphism and blood pressure levels in the case or control group. However, it showed that the TT homozygotes (n = 39) in obese patients had higher diastolic blood pressure levels than CC homozygotes (n = 47) or CT heterozygotes (n = 84) during pregnancy (p < 0.05). Conclusion: Our work does not provide evidence in favor of GNB3 C825T being a candidate gene for conferring genetic susceptibility to preeclampsia in a South West Chinese population.

Timing of Antibiotic Prophylaxis in Elective Caesarean Delivery: A Multi-Center Randomized Controlled Trial and Meta-Analysis

Objective To compare the effectiveness of antibiotic prophylaxis before skin incision with that after umbilical cord clamping in elective caesarean delivery. Methods We conducted a randomized open-label controlled trial with two parallel arms at three hospitals in western China. Participants meeting the inclusion criteria received antibiotics 30-60 minutes before skin incision while others received antibiotics after umbilical cords clamping. For the meta-analysis, studies were identified from the database of PUBMED, Cochrane Library and EMbase and assessed using the Cochrane risk of bias tool. Results Four hundred and ten patients were randomized to receive antibiotics before skin incision (n = 205) or after umbilical cords clamping (n = 205). There was no difference in the incidence of postpartum endometritis (RR = 0.34, 95% CI 0.04 to 3.24), wound infection (RR = 3.06, 95% CI 0.13 to 74.69) and total puerperal morbidity (RR = 1.02, 95% CI 0.47 to 2.22). No increase in the incidence of neonatal sepsis (RR = 0.34, 95% CI 0.04 to 3.24), septic workup (RR = 0.41, 95% CI 0.08 to 2.07), or intermediate NICU admission (RR = 0.73, 95% CI 0.24 to 2.26) was observed. The meta-analysis involving nine RCTs showed that no statistically significant difference was found in terms of the risk of postpartum endometritis (RR = 0.73, 95% CI 0.39, 1.36), wound infection (RR = 0.80, 95%CI 0.55, 1.17), or puerperal morbidity (RR = 0.89, 95% CI 0.70, 1.13). No increase in the incidence of neonatal sepsis (RR = 0.65, 95% CI 0.35 to 1.20), septic workup (RR = 0.88, 95% CI 0.50 to 1.54), or intermediate NICU admission (RR = 0.91, 95% CI 0.70 to 1.18) was observed. Conclusion For elective caesarean delivery, the effects of antibiotic prophylaxis before skin incision and after umbilical cord clamping were equal. Both antibiotic prophylaxis before skin incision and that after umbilical cord clamping were recommended for elective caesarean delivery. The outcome of further studies should address both maternal and neonatal infectious morbidity as well as long-term neonatal follow up. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-11001853

Diversified gut microbiota in newborns of mothers with gestational diabetes mellitus

Gestational diabetes mellitus (GDM), a high-risk pregnancy complication of great effect on the perinatal health of women and newborns, may cause changes of gut microbiota in mothers and further affect gut microbiota in newborns. This study aimed to investigate the potential effect of mother GDM on newborns’ gut microbiota. Meconium DNA was extracted from a total of 34 full-term and C-sectioned newborns, in which 20 newborns had mothers diagnosed with GDM, while 14 had unaffected mothers. Sequencing and bioinformatics analysis of 16S rRNA indicated that the gut microbiota of GDM newborns showed differences compared to control newborns. The taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the GDM group showing lower alpha-diversity than that of control group. The phyla of Proteobacteria and Actinobacteria in GDM newborns increased, while that of Bacteroidetes significantly reduced (P<0.05). Moreover, several unique gut microbiota in phylum of Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Chloroflexi, Acidobacteria, and Planctomycetes found in control newborns were absent in GDM ones. At genus level, the relative abundance of Prevotella and Lactobacillus significantly decreased (P<0.05) in GDM newborns. Correlation analysis indicated that maternal fasting glucose levels were positively correlated with the relative abundance of phylum Actinobacteria and genus Acinetobacter, while negatively correlated with that of phylum Bacteroidetes and genus Prevotella. However, bacteria in GDM grade A2 (GDM_A2) newborns did not show any statistical variation compared to those from control newborns, which might be attributed to the additional intervention by insulin. The results of this study have important implications for understanding the potential effects of GDM on the gut microbiota of newborns and thus possibly their metabolism at later stages in their lives.

Clinical assessment of the specificity of an adipsin rapid test for the diagnosis of preeclampsia

ABSTRACT Objective: To evaluate the specificity of the adipsin rapid test in clinical practice for the diagnosis of preeclampsia (PE). Methods: A total of 1144 pregnant women were recruited in this study: 44 pregnant women with PE and 1100 healthy pregnancies as controls. Urine samples were collected and used, respectively, for the adipsin rapid test and the urinary dipstick test for protein detection. Sensitivity and specificity were calculated on the basis of the detection results. Results: In the 1144 women examined with the adipsin rapid test for PE diagnosis, the sensitivity and specificity were 93.2% and 98.8%, respectively; the total accuracy was 98.6%. For the 1144 women tested with urinary dipstick, the sensitivity and specificity were 93.2% and 40.5%, respectively; and the total accuracy was 42.5%. Conclusion: Both the adipsin rapid test and the urinary dipstick test are noninvasive and inexpensive rapid tests for the diagnosis of PE. However, the adipsin rapid test was proven more reliable since it had a higher sensitivity, specificity, and accuracy.

Association study between -765G >c and - 119SG>A functional polymorphisms in the cyclooxygenase 2 gene and risk of preeclampsia

OBJECTIVE To investigate the relationship between two polymorphisms immediately upstream of the cyclooxygenase 2 (COX2) gene and preeclampsia in a South West Han Chinese population. METHODS Blood 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. RESULTS G 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. CONCLUSION COX2 -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.