Phd scholar, Liaquat university of medical and health sciences jamshoro
Vegf SNPs and serum levels association with preeclampsia in pakistanis
Preeclampsia is characterized by hypertension and proteinuria after 20th week of gestation. It has been associated with increased maternal and fetal morbidity and mortality. Number of studies have been conducted among various population on association of preeclampsia with genetic factors. However no research has been carried out so far in pakistani pregnant women relating genetic association. We have determined Vegf gene polymorphisms along with serum levels of vegf in preeclamptic women and compared it with normal pregnant women. Besides that we have developed cost effective genotyping method in our population which can later be used as genotyping and diagnosting tool for detection of Vegf gene polymorphisms.
Abstract: Preeclampsia is a common medical complication in pregnancy. It has been reported to be associated with decreased serum magnesium levels. However, there has not been evidence demonstrating utilization of change in magnesium for prediction of preeclampsia. The purpose of this study was to develop magnesium fraction-based equations which took other significant clinical risk factors into consideration for prediction of preeclampsia.We collected serum total and ionized magnesium ionized magnesium levels from 84 pregnant women diagnosed with preeclampsia after week 20 of pregnancy. The ionized magnesium fraction was then calculated by the percentage ratio of ionized and total magnesium level.Sixty-four (76.19%) women had normal pregnancy and 20 (23.81%) developed preeclampsia. The ionized magnesium fraction was significantly lower in preeclampsia group (23.95 ± 4.7% vs. 26.28 ± 2.3%, p = .04). Additionally, lower ionized magnesium fraction (24.67%), teenage and elderly primigravida were significantly associated with preeclampsia (OR = 4.41, 95% CI: 1.46-13.40, OR = 5.47, 95% CI: 1.85-35.42 and OR = 11.11, 95% CI: 1.09-113.78, respectively). Consequently, we attempted to develop ionized magnesium fraction-based equations calculate risk scores for preeclampsia. The area of ROC for predictive accuracy of the model was 0.77 (p < .001) and ROC suggested that the score of 0.27 would be a threshold for screening preeclampsia with 70% sensitivity and 81% specificity.Ionized magnesium fraction may have been appropriate for screening of preeclampsia. We suggested blood testing on total and ionized magnesium concentrations as well as calculation of ionized magnesium fraction in addition to routine antenatal care for better screening of the disease.
Pub.: 11 Jan '18, Pinned: 14 Jan '18
Abstract: Objective: To identify whether pregnancy outcomes vary by the severity of pulmonary hypertension. Methods: A retrospective study was conducted on 78 cases of pregnancies complained with pulmonary hypertension who delivered in the First Affiliated Hospital, Sun Yat-sen University from 2006 to 2016.The selected cases were divided into three groups according to severity of pulmonary hypertension: mild pulmonary hypertension group (mild PAH group) was defined as a mean pulmonary artery pressure 30-49 mmHg, moderate pulmonary hypertension (moderate PAH group) as mean pulmonary artery pressure 50-69 mmHg and severe pulmonary hypertension (severe PAH group) as mean pulmonary artery pressure 70 mmHg or greater.The clinical features, risk pregnant complication, maternal and neonatal outcomes were described between these three groups.Analysis of variance, Chi-square test was used for statistical analysis. Results: The average age of mild, moderate and severe PAH group were (31±5) years old, (31±5) years old and (27±3) years old, respectively (P=0.050). The rate of natural fertilization (P=0.414), parity (P=0.527) and gestational age (P=0.165) were similar in these three groups. In 78 pregnancies with pulmonary hypertension, 64.9% of pregnancies in mild PAH group was NYHA Ⅰ, 50.0% of moderate PAH group was NYHA Ⅱ and 54.5% of severe PAH group was NYHA Ⅲ(P<0.001). There was no significant difference in the incidence of gestational diabetes mellitus (GDM, P=0.589), preeclampsia (P=0.942), premature rupture of membrane (PROM, P=0.276), scarred uterus (P=0.493) and postpartum hemorrhage (P=0.424). The cesarean section rate was 84.2%, 90.0% and 63.6% in three groups (P=0.208). However, neuraxial anesthesia was performed in 82.5% of cases in mild PAH and 90.0% of cases in moderate PAH, while 27.3% of cases of severe PAH underwent neuraxial anesthesia (P<0.001). The fetal outcome was similar in there groups.But the rate of admission of NICU was significantly different in three groups (P=0.011). Conclusions: Maternal and neonatal outcomes was similar in different severity of pulmonary hypertension.But the severity of pulmonary hypertension affect the type of anesthesia.Close monitoring during pregnancy and timely termination of pregnancy can improve the outcome of pregnancy.
Pub.: 13 Jan '18, Pinned: 14 Jan '18
Abstract: Ischemia-modified albumin (IMA) has been widely accepted as a serological biomarker. IMA has been proposed as a simple and novel marker of oxidative stress in preeclampsia (PE). This systematic review and diagnostic test accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel serological biomarker, IMA to detect PE.A systematic search of major databases was performed to identify all published diagnostic accuracy studies on IMA. Risk of bias and applicability concerns were asses for included studies. Summary estimates; the pooled sensitivity, specificity and the diagnostic odds ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects models. The overall test performance was summarized using summary receiver operating characteristic (SROC) curve analysis.Six articles were included in this meta-analysis. The overall estimates of IMA in detecting PE were: pooled sensitivity; 0.80 (95% CI 0.73-0.86), pooled specificity; 0.76 (95% CI 0.70-0.81), DOR; 14.32 (95% CI 5.06-40.57), and area under curve (AUC); 0.860. There was no between-study heterogeneity due to threshold effect.This meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy (AUC = 0.860). However, further research is needed for re-evaluation and clinical validation of fairly promising results of this meta-analysis.
Pub.: 13 Jan '18, Pinned: 14 Jan '18
Abstract: Preeclampsia (PE) is considered to be initiated by abnormal placentation in early pregnancy and results in systemic endothelial cell dysfunction in the second or third trimester. MicroRNAs (miRs) expressed in the human placenta can be secreted into maternal circulation via exosomes, which are secreted extracellular vesicles that serve important roles in intercellular communication. The present study hypothesized that upregulation of placenta‑associated serum exosomal miR‑155 from patients with PE may suppress endothelial nitric oxide synthase (eNOS) expression in endothelial cells. The results demonstrated that placenta‑associated serum exosomes from patients with PE decreased nitric oxide (NO) production and eNOS expression in primary human umbilical vein endothelial cells (HUVECs). Subsequently, an upregulation of placenta‑associated serum exosomal miR‑155 was detected in patients with PE compared with in gestational age‑matched normal pregnant women. In addition, the results demonstrated that overexpression of exosomal miR‑155 from BeWo cells was internalized into HUVECs, and was able to suppress eNOS expression by targeting its 3'‑untranslated region. The results of the present study indicated that placenta‑associated serum exosomes may inhibit eNOS expression in endothelial cell during PE development in humans, and this phenomenon may be partly due to increased miR‑155 expression in placenta‑associated serum exosomes.
Pub.: 13 Jan '18, Pinned: 14 Jan '18
Abstract: It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the decidua during early pregnancy compared to the secretory phase endometrium (non-pregnant), with a significant increase in M2 macrophage markers, suggesting that M2 is the predominant macrophage phenotype in the decidua. However, decidual samples from preeclamptic pregnancies showed a significant shift in macrophage phenotype markers, with upregulation of M1 and downregulation of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage migration and induced M1 macrophages to shift to an M2 phenotype. Moreover, treatment with conditioned media from decidualized ESCs induced changes in macrophage migration and polarization similar to that of VEGF treatment. These effects were abrogated by the addition of a potent VEGF inhibitor. Together these results suggest that decidual VEGF plays a significant role in macrophage recruitment and M2 polarization, and that inhibition of VEGF signaling may contribute to the shift in macrophage polarity observed in different pregnancy disorders, including preeclampsia.
Pub.: 13 Jan '18, Pinned: 14 Jan '18
Abstract: To investigate the association of angiotensinogen (AGT) gene polymorphisms and angiogenic factors with preeclampsia (PE) in Chinese women.A study on Chinese women was performed. Detection of the M235T polymorphism of AGT gene was carried out by PCR. Using a χ² test, genotype and allele frequencies were compared in all groups. Maternal serum levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt1) at gestation were compared between 92 women with PE and 100 controls by ELISA.Compared to the controls, the AGT homozygous of TT genotype in PE occurred significantly more frequently and the T allele was observed to occur more frequently than the M allele (p < 0.05). sFlt1 was present in high quantities in the serum of women with PE and was associated with low levels of free VEGF and PlGF (p < 0.05). Plasma sFlt1 levels are higher in PE patients with TT heterozygotes compared with MM homozygotes, but PIGF is lower (p < 0.05). Plasma VEGF concentrations showed no significant difference.Our study showed that AGT M235T polymorphism is associated with PE in Chinese women. Furthermore, the gene polymorphism of the components of the renin-angiotensin system may contribute to the concentration alterations of sFlt1, VEGF, and PlGF in maternal serum, which causes disordered vasculogenesis contributing to PE.
Pub.: 19 Jul '13, Pinned: 19 Dec '17
Abstract: Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual's susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk.A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08-2.12) or -634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03-1.50) was associated with the risk of PE, whereas there was no association between -2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82-1.16) or -1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94-1.78) polymorphism and PE risk in our study.Our meta-analysis suggested that VEGF -2578C/A or -1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or -634G/C polymorphism and risk of PE.
Pub.: 14 Nov '13, Pinned: 19 Dec '17
Abstract: Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the -670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.
Pub.: 06 Jul '14, Pinned: 19 Dec '17