PP005. Natriuretic peptide precursor B gene (TTTC)N microsatellite polymorphism and elevated BNP levels in early onset pre-eclampsia

Abstract

There is a variable tandem repeat (TTTC) polymorphism in the 5(')-flanking region of the natriuretic peptide precursor B gene (NPPB), which shows association with severe pre-eclampsia. The 11-repeat carrier frequency is significantly higher in severe pre-eclamptic patients. The 11/11 genotype carriers in the pre-eclamptics has significantly higher BNP levels. Our aim was to identify this polymorphism in samples of early onset pre-eclamptic (EOP) patients, late onset pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations. Blood samples were collected from healthy pregnant normotensive women (n=235) and women with pre-eclampsia (n=220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The plasma BNP concentration was measured by fluorescence immunoassay method using Triage BNP (Alere, San Diego). We detected 12 different repeats on the NPPB gene. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The 11/11 genotype carriers showed a significantly higher frequency in early onset pre-eclamptic patients than in the healthy pregnant controls (p=0.026). Calculated odds ratio (OR) was 1.694 (95% CI: 1.06-2.70). In contrast the 11/11 genotype carrier frequency was not significantly higher in the late onset pre-eclamptic group than in the control group (p=0.5308), adjusted OR 1.22 (95% CI: 0.7138-2.086). In the early onset pre-eclamptics the 11/11 genotype showed a significantly higher frequency than in the late onset group (p=0.0039) OR: 6.00. The concentration of the BNP was 9.75pg/ml in the healthy controls and 32.40pg/ml in the pre-eclamptic group (p<0.0001). The 11/11 genotype carriers had significantly higher BNP levels in the pre-eclamptic group. The early onset pre-eclamptic patients had a significantly higher BNP concentration (40.55pg/ml) than in the late onset pre-eclamptic patients (24.1pg/ml) (p=0.013). The NPPB gene (TTTC) microsatellite polymorphism in the 5(')-flanking region showed a significant difference in the distribution of alleles and genotypes between early onset and late onset pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in early onset pre-eclamptic women, and it showed association with the genotypes.