Pre-eclampsia (PE) is a common pregnancy disorder clinically diagnosed by de novo hypertension and proteinuria developing after 20 weeks’ gestation. Women with a familial history have an increased risk of developing PE. We have previously identified candidate maternal susceptibility genes through genetic studies in Australian/New Zealand families (1-4).
The aims were to determine mRNA levels of maternal susceptibility genes in gestation matched third trimester decidual tissue of normotensive (n=8) and severe PE [SPE defined according to (5), n=7] pregnancies and correlate mRNA levels with the clinical severity of SPE.
Decidua basalis samples were archived laboratory cDNA samples derived from extracted RNA. Relative mRNA levels of ACVR1, INHA, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 were determined by real-time PCR. Relative mRNA levels were then correlated with various clinical parameters associated with SPE. Parameters assessed were highest recorded systolic and diastolic blood pressures, highest recorded degree of proteinuria, lowest recorded platelet levels, onset of SPE, gestation at delivery, infant weight percentiles, treatment with anti-convulsants and number of anti-hypertensive medications.
The relative mRNA levels of ACVR1, ERAP1, ERAP2, LNPEP and COL4A2 were significantly increased in SPE compared with normotensive patients by 21.4, 5.4, 20.4, 12.9 and 15.2 fold respectively (p<0.05, Mann-Whitney U test). Increased relative mRNA levels of INHA, INHBB and COL4A2 were significantly associated with earlier delivery (p<0.05, Spearman’s correlation). An increased mRNA level of COL4A2 was also associated with earlier PE onset (p<0.05, Spearman’s correlation).
These data show differential relative mRNA levels of five candidate maternal PE susceptibility genes and negative correlations with delivery and PE onset. The data suggest altered gene expression of maternal susceptibility genes may play roles in the development of PE and the clinical course of disease severity. The roles that these genes may play in PE development and its subsequent severity will be further investigated.