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Correlation Of The Rs9904341and Rs1042489of Survivin Gene With Pre-eclampsia

Posted on:2014-02-05Degree:MasterType:Thesis
Country:ChinaCandidate:X G QiaoFull Text:PDF
GTID:2234330398977446Subject:Obstetrics and gynecology
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Background and Objective:Pre-eclampsia,which includes mild pre-eclampsia and severe pre-eclampsia,is a common type of hypertensive disorders in pregnancy.In the worldwide,the incidence rate of pre-eclampsia is2%to3%, and it is much more in the developing than in the developed country.Pre-eclampsia seriously affect the health of both the mother and the fetus.On the one hand, it can lead to the acute renal failure, the liver injury, intracranial hemorrhage, pulmonary edema, and even the death to the pregnant women. On the other hand,it can cause the premature birth or the fetal growth restriction to the featus.At the present,the etiology and pathogenesis of pre-eclampsia hasn’t been clear. Many studies suggest that pre-eclampsia could be a systemic disease, and there are many reasonable theory to explain why it occurred. Some people think that trophoblast cells can invade the muscular layer of uterus to cause pre-eclampsia,however,other people think that pre-eclampsia is related to immune mechanisms, vascular endothelial cell damage, genetic factors, insulin resistance and so on.The impact of genetic factors for pre-eclampsia becomes a hotspot in the recent years.Many studies have shown that pre-eclampsia has a genetic predisposition at home and abroad. Many genes which could affect maternal blood pressure, blood volume, placental tissue, vascular endothelial function,vascular re-cast maybe affect the cause of pre-eclampsia.Single nucleotide polymorphism(SNP) is that a single nucleotide variations could change the DNA sequence at the genomic level.With the development of science and technology, the detection and analysis techniques of the single nucleotide polymorphism can contribute to improve its ability to locate genes related to some disease, especially to be suitable for the disease affected by some genes.Now people have found multiple gene loci of single nucleotide polymorphisms in correlation with the incidence and the state of pre-eclampsia,for example:osteoprotegerin gene, vascular endothelial growth factor, human leukocyte differentiation antigen and so on.Survivin is an inhibitor of apoptosis gene, which encodes a protein with a role of inhibition of apoptosis and regulation of the cell cycle.In the area of oncology, the single nucleotide polymorphism of survivin may affect the risk of some tumor and its genetic susceptibility.The protein and mRNA encoded by survivin can be detected in the embryo and the fetal tissue. Most studies have confirmed that the protein and mRNA encoded by survivin in the placental tissue were significantly less in the pre-eclampsia group than the result in the normal group.It’s all the same with the severity of the disease.Many studies have shown that there are many single nucleo tide polymorphisms (SNPs) in the coding and the nocoding region of survivin. These SNPs can affect the expression and regulation of survivin in some diseases, there is no special report on whether SNP of survivin affect the pathogeny and severity of pre-eclampsia now.Analysising the distribution of the gene type of survivin in the normal pregnant women and the pre-eclampsia,we study whether the rs9904341and rs1042489of survivin is associated with the pathogenesis and severity of pre-eclampsia.Materials and methods:1. Materials:We select96women with pre-eclampsia, including52women with mild pre-eclampsia and44women with severe pre-eclampsia, and110pregnant women without pre-eclampsia.All research objects had came to the secondhospital affiliated to zhengzhou university or the maternity and child care centers of zhengzhou city for antenatal examination and delivery from July2011to March2012.We confirm patients with preeclampsia based on medical history,clinical manifestations and biochemical test results.All objects of study were single births and the first pregnancy without diabetes, heart disease, chronic hypertension, and other pregnant complications.They also had no blood relationship and were the Han nationality.Their husband were all the Han nationality.At last,they live in Zhengzhou or the surrounding areas for a long time.The age of pre-eclampsia group is from18to38and the average age is30.83±4.71.The gestational weeks of preeclampsia group is from25weeks to40weeks and the average gestational weeks is36.22±2.94weeks.The age of control group is from16to40and the average age is30.64±4.52.The gestational weeks of pre-eclampsia group is from34weeks to40weeks and the average gestational weeks is36.73±2.53weeks.2. Methods:We subject to the approval of pregnant women wo needed and then collected2ml venous blood from the elbow of each women before breakfast using EDTA anticoagulant tubes.These blood were stored in the refrigerator at-80℃.By PCR-RFLP,we detect the distribution of the gene type of survivin in the normal pregnant women and the pre-eclampsia and its distribution in the mild preeclampsia and the severe pre-eclampsia patients.3.The analysis and comparision of statisticsWith the help of SPSS17.0system, which is a good statistical analysis software, measurement data results are showned as mean±standard (x±s) in each group. We ananlysis the diversity of measuring material of each group by ANOVA and dicuss the gene type and allelic genes between groups by RxC table.Acoording to Hardy-Weinberg equilibrium(HWE),the distribution of gene type was tested whether it is a good representative or not.Genetic equilibrium analysis.The judgement standard is a=0.05and P<0.05.Results:1The clinical data results of the pre-eclampsia group and the normal groups analysed by SPSS17.0..Between women with pre-eclampsia and the control group,the comparision of age, stature and gestational weeks is not significantly different(P<0.05). On the contary,the weight of the object study,the BMI before gestation and the BMI of the third trimester is significant difference(P>0.05).2The comparision and analysis of gene type of rs9904341of Survivin in the pre-eclampsia and the control groups and that of rs1042489.Acoording to Hardy-Weinberg equilibrium,the two polymorphism distribution of object of study have a suitable group representation by chi-square test of goodness of fit.2.1The statistical analysis of the distribution of genotype and allele frequency of rs9904341(1) The statistical results of genotype and allele by SPSS17.0to the object of pre-eclampsia and the object without pre-eclampsia:In the object of pre-eclampsia group,the CC percentage is16.7%,the CG percentage is46.9%, the GG percentage is36.5%,the C allele percentage is40.1%,and the allele G percentage is59.9%.In the objet of control group,the CC percentage is26.4%,the CG percentage is49.1%, the of GG percentage is24.5%,the C allele percentage is50.9%,and the G allele percentage is49.1%.The diversity percentage allele G genotype has a statistical significance between the two groups(P<0.05).Correlation of the SNP and the risk of pre-eclampsia is analysed.Analysis of data is showed that the odds ratio (OR) of G/C is1.549and its95%confidence interval (95%CI) is1.047~2.291.(2)The statistical results of genotype and allele by SPSS17.0to the object of mild pre-eclampsia and the object with severe pre-eclampsia:In the object of mild pre-eclampsia group,the CC percentage is19.2%,the CG percentage is59.6%, the GG percentage is21.2%,the C allele percentage is49.0%,and the allele G percentage is51.0%.In the objet of severe pre-eclampsia group,the CC percentage is13.6%,the CG percentage is31.8%, the GG percentage is54.5%,the C allele percentage is29.5%,and the G allele percentage is70.5%.The diversity percentage allele G genotype has a statistical significance between the two groups(P<0.05).2.2The statistical analysis of the distribution of genotype and allele frequency of rs1042489(1)The statistical results of genotype and allele by SPSS17.0to the object of pre-eclampsia and the object without pre-eclampsia:In the object of pre-eclampsia group,the CC percentage is18.8%,the CT percentage is58.3%, the TT percentage is22.9%,the C allele percentage is47.9%,and the allele T percentage is52.1%.In the objet of control group,the CC percentage is12.7%,the CT percentage is54.5%, the TT percentage is32.7%,the C allele percentage is40.0%,and the T allele percentage is60.0%.The difference of frequency of genotype and allele has no statistical significance between the two groups(P>0.05).(2) The statistical results of genotype and allele by SPSS17.0to the object of mild pre-eclampsia and the object with severe pre-eclampsia:In the object of mild pre-eclampsia group,the CC percentage is19.2%,the CT percentage is57.7%, the TT percentage is23.1%,the C allele percentage is48.1%,and the allele T percentage is51.9%.In the objet of severe pre-eclampsia group,the CC percentage is18.2%,the CT percentage is54.5%, the TT percentage is27.3%,the C allele percentage is45.5%,and the T allele percentage is54.5%.The difference of frequency of genotype and allele has no statistical significance between the two groups(P>0.05).Conclusion:1The G allele of rs9904341of survivin may be a genetic risk factor of pre-eclampsia for women of the Han nationality in the central plains and it may also be associated with its severity.2The rs1042489of survivin may have no correlation with pre-eclampsia in the women of Han nationality in the central plains.
Keywords/Search Tags:Survivin, Polymorphism, Pre-eclampsia
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