Evaluation of the angiogenic factors sFlt-1, PlGF, and the sFlt-1/PlGF ratio in preeclampsia and associated features.

PROBLEM: Soluble Fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF) were previously reported to play a key role in the pathogenesis of preeclampsia (PE). We tested the link between altered PlGF and sFLT-1 levels, and their ratio (sFlt-1/PlGF) with PE and PE-associated featured in Tunisian PE cases and age- and BMI-matched normotensive women. METHOD OF STUDY: Peripheral blood specimens from 88 women with PE, and 60 control women were tested for PlGF and sFLT by commercially available ELISA. RESULTS: Significant increases in sFlt-1 levels and in the sFlt-1/PlGF ratio, more than changes in PlGF levels were noted in PE subjects when compared to control women. Elevation in sFlt-1 and sFlt-1/PlGF ratio was observed at different percentile values in PE cases. The receiver operating characteristic (ROC) area under the curve (AUC) for sFlt-1, PlGF, and sFlt-1/PlGF ratio were 0.869 ± 0.031, 0.463 ± 0.048, and 0.759 ± 0.039, respectively. A systematic shift in sFlt-1, but not in PlGF, distributions for higher values occurred in PE subjects. A progressive increase in the adjusted OR paralleled increased sFlt-1 and the sFlt-1/PlGF ratio percentile values; no similar trend was noted for the PlGF percentiles. Increased sFlt-1 levels and sFlt-1/PlGF ratio were significantly correlated with dysmenorrhea, hypertension, baby weight, and C-section. In contrast, no correlation was found between PlGF and the PE-associated features tested. CONCLUSIONS: Increased sFlt-1 levels and corresponding sFlt-1/PlGF ratio, but not circulating PlGF levels, constitute an independent risk factor for PE.

MMP-2 and MMP-9 Polymorphisms and Preeclampsia Risk in Tunisian Arabs: A Case-Control Study.

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case-control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

Impact of obesity on the association of active renin and plasma aldosterone concentrations, and aldosterone-to-renin ratio with preeclampsia.

OBJECTIVE: To evaluate the association of active renin concentration (ARC), plasma aldosterone concentration (PAC) and aldosterone-to-renin ratio (ARR) with the risk of preeclampsia (PE), in particular according to the status of obesity. DESIGN: This retrospective case-control study involved 90 women with PE (mean gestation 35.6 ±â€¯3.6 weeks) and 90 age-matched control women with uncomplicated pregnancies (mean gestation 38.5 ±â€¯2.5 weeks). ARC and PAC were measured by radioimmunoassay; ARR calculated as PAC to ARC ratio. PE cases were stratified into 5 percentiles groups, and analyzed in multivariate logistic regression. RESULTS: Women with PE had significantly lower median ARC and PAC than control women, which were confirmed by percentiles analysis. Spearman correlation demonstrated negative correlation of ARC with body mass index, systolic/diastolic blood pressure. PAC correlated negatively with systolic/diastolic blood pressure, but positively with baby weight, ARC and ARR. On the other hand, ARR positively correlated with BMI and PAC, but negatively with ARC. Lower PAC was associated with PE, irrespective of body weight, while ARC levels were significantly lower in non-obese PE cases vs. control women. ARR was not significantly different between PE cases and control women, when stratified according to obesity. CONCLUSION: Low ARC and PAC in third trimester are more strongly associated with preeclampsia respectively in non-obese and obese women.