Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia

Background: There is a variable tandem repeat polymorphism in the 5'-flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension. Our aim was to identify this polymorphism in samples of pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations.

Methods: 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.

Results: We detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The number of 10-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnant controls (p=0.032). After adjustment for confounding factors pre-pregnancy BMI, maternal age, primiparity and smoking, the calculated odds ratio (OR) was 0.19 (95% CI: 0.04-0.87). Similarly, the 12-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnants (p=0.037; adjusted OR: 0.53 (95% CI: 0.29-0.96)). In contrast the 11-repeat genotype carrier frequency was significantly higher in the pre-eclamptic than in the healthy pregnant group (p<0.001; adjusted OR 2.91 (95% CI: 1.75-4.84)). 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 both groups.

Conclusions: The NPPB gene (TTTC) microsatellite polymorphism in the 5'-flanking region showed significant difference in the distribution of alleles and genotypes between healthy pregnant controls and pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in pre-eclamptic women, and it showed association with the (TTTC) genotypes. We introduced an F-PCR and DNA fragment analysis method for the fast and reliable detection of this STR.