Szabó G, Molvarec A, Nagy B, Rigo J
First Departement of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Pregnancy Hypertens. 2012 Jul;2(3):242-3. doi: 10.1016/j.preghy.2012.04.116. Epub 2012 Jun 13.
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.
利钠肽前体B基因（NPPB）5′侧翼区存在可变串联重复序列（TTTC）多态性，该多态性与重度子痫前期相关。重度子痫前期患者中11重复序列携带者频率显著更高。子痫前期患者中的11/11基因型携带者的脑钠肽（BNP）水平显著更高。
我们的目的是在早发型子痫前期（EOP）患者、晚发型子痫前期患者和健康对照的样本中鉴定这种多态性。我们还比较了利钠肽B（BNP）浓度。
采集健康妊娠血压正常女性（n = 235）和子痫前期女性（n = 220）的血样。提取DNA，进行荧光PCR和DNA片段分析以检测（TTTC）重复序列。采用Triage BNP（Alere，圣地亚哥）通过荧光免疫分析法测定血浆BNP浓度。
我们在NPPB基因上检测到12种不同的重复序列。对照组和子痫前期组之间等位基因和基因型的总体分布存在显著差异。11/11基因型携带者在早发型子痫前期患者中的频率显著高于健康妊娠对照组（p = 0.026）。计算的优势比（OR）为1.694（95%可信区间：1.06 - 2.70）。相比之下，晚发型子痫前期组中11/11基因型携带者频率在统计学上并不高于对照组（p = 0.5308），校正OR为1.22（95%可信区间：0.7138 - 2.086）。在早发型子痫前期患者中，11/11基因型的频率显著高于晚发型组（p = 0.0039），OR为6.00。健康对照组中BNP浓度为9.75pg/ml，子痫前期组为32.40pg/ml（p < 0.0001）。子痫前期组中11/11基因型携带者的BNP水平显著更高。早发型子痫前期患者的BNP浓度（40.55pg/ml）显著高于晚发型子痫前期患者（24.1pg/ml）（p = 0.013）。
在一个种族同质的人群中，5′侧翼区的NPPB基因（TTTC）微卫星多态性在早发型和晚发型子痫前期患者之间的等位基因和基因型分布存在显著差异。早发型子痫前期女性的BNP浓度更高，且与基因型相关。
