title: Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia.
abstract: 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.
authors.affiliation: 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Attila
authors.initials: A
authors.lastname: Molvarec
authors.forename: Balázs
authors.initials: B
authors.lastname: Stenczer
authors.forename: János
authors.initials: J
authors.lastname: Rigó
authors.forename: Bálint
authors.initials: B
authors.lastname: Nagy
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics*; D011247:Pregnancy; D011498:Protein Precursors / Q000097:blood / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain