Nagy Bálint, Savli Hakan, Molvarec Attila, Várkonyi Tibor, Rigó Barbara, Hupuczi Petronella, Rigó János
1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Clin Chim Acta. 2008 Mar;389(1-2):126-31. doi: 10.1016/j.cca.2007.12.003. Epub 2007 Dec 7.
The vascular endothelial growth factor (VEGF) has a critical role in vasculogenesis and vascular permeability in several diseases including preeclampsia. There are at least 30 single nucleotide polymorphic (SNP) places on this gene. VEGF G+405C, C-2578A and C-460T SNPs are known to be related to VEGF production. VEGF polymorphisms were studied in preeclampsia, but not in HELLP syndrome. Therefore, we decided to determine the allele and genotype frequencies of VEGF G+405C, C-460T and C-2578A SNPs in healthy pregnant women and HELLP syndrome patients.
The authors introduced a quantitative real-time PCR method for the determination of the three VEGF SNPs. Blood samples were collected from 71 HELLP syndrome patients and 93 healthy controls. DNA was isolated by using silica adsorption method. The SNPs were determined by quantitative real-time PCR and melting curve analysis using LightCycler.
There were significant differences in the allele and genotype frequencies of VEGF C-460T SNP between the two study groups. The T allele was present in 71.1% in the HELLP group, while in 53.8% in the controls (p=0.0014). The TT genotype occurred significantly more frequently in the HELLP group than in the control group (45.1% vs. 21.5%; p (for genotype frequencies)=0.0011). The TT genotype carriers had an increased risk of HELLP syndrome, which was independent of maternal age and primiparity (adjusted odds ratio (OR)=3.03, 95% confidence interval (CI)=1.51-6.08; p=0.002). Although the VEGF G+405C allele and genotype distributions did not differ significantly between the two groups, the CC genotype carriers were also found to have an increased risk for HELLP syndrome after adjustment for maternal age and primiparity (adjusted OR=3.67, 95% CI=1.05-12.75; p=0.041). The VEGF C-2578A SNP was not associated with HELLP syndrome.
The quantitative real-time PCR combined with melting curve analyses is a fast and reliable method for the determination of VEGF SNPs. We found that the VEGF -460TT and +405CC genotype carriers have an increased risk of HELLP syndrome. As these two SNPs were previously observed to be related to production of the VEGF protein, we suppose that these VEGF polymorphisms -- interacting with other genetic and environmental factors - could play a role in the development of HELLP syndrome.
血管内皮生长因子(VEGF)在包括子痫前期在内的多种疾病的血管生成和血管通透性中起关键作用。该基因上至少有30个单核苷酸多态性(SNP)位点。已知VEGF G+405C、C-2578A和C-460T SNP与VEGF产生有关。已对子痫前期中的VEGF多态性进行了研究,但未在HELLP综合征中进行研究。因此,我们决定确定健康孕妇和HELLP综合征患者中VEGF G+405C、C-460T和C-2578A SNP的等位基因和基因型频率。
作者引入了一种定量实时PCR方法来测定三种VEGF SNP。从71例HELLP综合征患者和93例健康对照者中采集血样。使用硅胶吸附法分离DNA。通过定量实时PCR和使用LightCycler的熔解曲线分析来确定SNP。
两个研究组之间VEGF C-460T SNP的等位基因和基因型频率存在显著差异。HELLP组中T等位基因的出现频率为71.1%,而对照组中为53.8%(p=0.0014)。HELLP组中TT基因型的出现频率显著高于对照组(45.1%对21.5%;p(基因型频率)=0.0011)。TT基因型携带者患HELLP综合征的风险增加,这与产妇年龄和初产情况无关(调整后的优势比(OR)=3.03,95%置信区间(CI)=1.51-6.08;p=0.002)。虽然两组之间VEGF G+405C等位基因和基因型分布没有显著差异,但在调整产妇年龄和初产情况后,CC基因型携带者患HELLP综合征的风险也增加(调整后的OR=3.67,95%CI=1.05-12.75;p=0.041)。VEGF C-2578A SNP与HELLP综合征无关。
定量实时PCR结合熔解曲线分析是一种快速可靠的测定VEGF SNP的方法。我们发现VEGF -460TT和+405CC基因型携带者患HELLP综合征的风险增加。由于此前观察到这两个SNP与VEGF蛋白的产生有关,我们推测这些VEGF多态性——与其他遗传和环境因素相互作用——可能在HELLP综合征的发生发展中起作用。