| Objective:Hypertensive disorder complicating pregnancy, clinically manifested as hypertension and proteinuria, is a special disease in period of pregnancy leading to convulsion, coma, even maternal and fetus death. It is a leading cause of maternal and perinatal morbidity and mortality. The morbidity is 9.4% in China and 7-12% abroad. Pre-eclampsia is a serious stage of the disease. Now both in China and other developed countries of Europe and America, Severe pre-eclampsia accompanying serious complications is among the top three leading causes of maternal death. Genetic factor is one of the causes of hypertensive disease complicating pregnancy, because patients with a family medical history are more likely to suffer from gestational hypertension. A great deal of research about pre-eclampsia pathogenesis and pathophysiology shows that pre-eclampsia is a multifactorial disease, in which environmental and genetic factors play an important role. Some scholars have proposed a unified theory:genetic factors, inflammation, immunologic tolerance and trophoblast hypoxia all lead to the vessel endothelium dysfunction, eventually trigger pre-eclampsia. Many pathogenesis have been described about etiology of the disorder and the uterine placenta ischemia theory. The uterine placenta hypoxia theory, blood vessel endothelium dysfunction theory have been universally accepted. It is accepted that superficial implantation of placenta and poorly transformed spiral arteries. Some investigations indicate that endothelial dysfunction and defective endovascular invasion of cytotrophoblast are central etiology and pathology of hypertensive disorder complicating pregnancy. Recent data suggest that VEGF,PIGF-. sFlt-1 have been implicated in the pathophysiology of hypertensive disorder complicating pregnancy and can be as a index to predicte and diagnosis preeclampsia. We investigated the sFlt-1,PIGF in peripheral blood of patients with preeclampsia to explore the relationship between sFlt-1,PIGF with pre-eclampsia, their diagnostic value in preeclampsia. and the relationship between single nucleotide polymorphisms(SNPs) of vascular endothelial growth factor (VEGF) and susceptibility of preeclampsia patients. The aim of our study is to investigate the frequency of SNPs in VEGF gene at site+936 and-634 in Han nationality and its role in the pathogenesis of the PE.Methods:1. Select 36 female patients with PE (including 15 subjects with mild preeclampsia,21 subjects with severe pre-eclampsia) and 17 others without pre-eclampsia as study groups and control group respectively. The cases come from department of gynaecology and obstetrics of Shenzhen Maternity and Child Healthcare Hospital from February 2009 to April 2010; The serum levels of sFlt-1 and PLGF were detected by enzyme linked immunosorbent assay technique. Blood samples were obtained for DNA analysis and sequencing analysis of SNP at+936 and-634.105 pergnnacy women(104 have VEGF+936PCR product) 43 cases of patients with PE and 61 cases of health control women random selected were studied from February to December in 2010. and other 104 have VEGF-634PCR product including 42 female patients with PE (including mild preeclampsia and severe pre-eclampsia) and 62 normal pregnancy without pre-eclampsia,analysed the relationship between the polymorphisms of VEGF+936,-634 and preeclampsia.They are all single pregnancies in han national.Results:1. The serum level of sFlt-1 of patients with PE was (5561.40±5336.73) ng/L, The serum level of mild preeclampsia group was (3854.47±3013.44) ng/L, The serum level of severe preeclampsia was (6780.63±6303.86) ng/L, The serum level of control group is (2761.20±2119.42) ng/L. The results showed that the serum sFlt-1 levels of PE group were relatively higher than those of control group (P<0.05), and that there were significant differences between the severe preeclampsia group and the mild group.2. The serum PIGF of patients with PE was (46.95±33.41) ng/L, the figure of mild preeclampsia group was (62.41±38.86) ng/L, the figure of severe preeclampsia group was (35.91±24.28) ng/L, the figure of control group was (147.55±86.66) ng/L. The results showed that the serum PIGF levels of PE group were relatively lower than those of control group (P＜0.05), and that there were significant differences among the mild preeclampsia group, severe preeclampsia and control group.3. The ratio of the sFlt-1 concentration and the PIGF in serum of PE is relatively higher than that of control group (P＜0.05) and there were significant differences among the mild preeclampsia, severe preeclampsia and control group. (P <0.05)4. ROC of sFlt-1,PIGF,sFlt-1/P1GF,serum uric acid. Area under the curve of sFlt-1,PIGF,sFlt-1/P1GF and serum uric acid are respectively 0.65,0.913,0.908 and 0.788. Area under the curve of PIGF is the biggest and statistically significant. When the cut-off is 107.25ng/L, sensitivity is 91.7%, specificity is 82.4%.From the ROC curve, we can see that the specificity and sensitivity of PIGF is the highest, better than serum uric acid. 5. There were significant differences in the distribution frequency of allele C, T on VEGF+936 gene and genotypes between preeclampsia group and control group (X2=5.459=, P=0.043). the frequency of+936CT and TT genotype between preeclampsia group and control group are 48.8% vs 29.5%; 4.7% vs 1.6%, CC genotypes 46.5% in PE group is lower than that of the control group 68.9%. frequency of VEGF+936 allele C in PE group is lower than that of the control group (70.9% vs83.6%, but allele T is higher than that of the control group (29.1% vsl9.4%) (X2=4.781,P=0.029). CT+TT genotype is higher than that of the control group (53.5% vs31.1%),but CC genotype is that of the lower than control group (46.5% vs68.9%. (X2=5.229,P=0.022). There are significant differences.6. With odds ratio(OR) calculate VEGF+936 genotypes In preeclampsia relative risk, the risk ratio of pre-eclampsia cases with CT/TT genotypes was 2.542 times higher than that with CC genotype 95% confidence interval (1.133,5.703). The risk ratio of preeclampsia cases with allele T was 2.09 times higher than that with allele C95% confidence interval (1.072,4.077)7.There was no significant difference in the distribution frequency of allele C, T on VEGF-634 gene and genotypes between preeclampsia group and control group (Fisher's Exact Test X2=2.451, P=0.329>0.05). the frequency of-634 GC and CC genotype between preeclampsia group and control group are 31.0% vs 11.9%; 25.8% vs 4.8%, GG genotypes57.1% in PE group is lower than control group 69.4%, (P>0.05). frequency of VEGF-634 allele G in PE group is lower than control group (73% vs82%), but allele C is higher than control group (27% vs18%) (Pearson chi-square X2=4.781,P=0.029<0.05). CT+TT genotype is higher than control group (53.5% vs31.1%), but CC genotype is lower than control group (46.5% vs68.9%). (Pearson chi-square X2=2.744, P=0.098P>0.05) There are significant differences. Conclusion:1. The serum sFlt-1 levels of each PE groups were relatively higher than those of control group. SF1t-1 may be related to PE.2. The serum P1GF levels of each PE groups were relatively lower than those of control group. There may be an association between PE and PLGF.3. The ratio of the sFlt-1 concentration and the P1GF levels in serum of pre-eclampsia groups were relatively higher than that of control group. Disequilibrium of sFlt-1/P1GF may contribute to PE.4. The serum P1GF has a very good diagnostic value, specificity and sensitivity of P1GF is better than serum uric acid.5. The serum P1GF<107.25ng/L has preeclampsia diagnostic meaning.6. We concluded that SNP at+936 sites have a high possibility of significant associations with the pathogenesis of PE.7.CC may have protectiveness on the pathology of PE.8.SNP at-634 site did not contribute to PE. |
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