Dissertation
Dissertation > Medicine, health > Obstetrics and Gynaecology > Obstetrics > Pathological pregnancy ( abnormal pregnancy )

Relationship between the Single Nucleotide Polymorphism of the Untranslated Region of HLA-G and Preeclampsia

Author ZhangZuo
Tutor ZhangZhan
School Zhengzhou University
Course Obstetrics and Gynaecology
Keywords Pre-eclampsia HLA-G 3’-UTR Single-nuleotidepolymoephisms allele genotype genotype compatibility
CLC R714.2
Type Master's thesis
Year 2011
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Pre-eclampsia is a type of Hypertensive disorder complicating pregnancy (HDCP).It follows high blood pressure、albuminuria and dropsy after the 20th gestational week.Then it is together with many damages of the organ dirty machines of the whole body.In recent years,there is many pathogenesis of pre-eclampsia,up to now still no hard conclusion.Most research at home and abroad is focus on the etiology and pathogenesia of pre-eclampsia and eclampsia,and it has several theoties as follows:Genetics、immunity doctrine、placenta to lack blood theory and oxidation.Among them,the most famous theory that is connecting with abnormality of imunity tolerance.Human leukocyte antigen(HLA) is Major Histocompatibility Complex(MHC).It is mainly expressed on the maternal-fetal interface extravillous cytotrophoblasts (EVCT). Its rigorous histological distribution and the immune tolerance is playing an important role in during pregnancy. HLA-G is one molecule of immune tolerance, it can through many mechanisms involved in the immune tolerance.involved in induction and maintenance of immune tolerance,and HLA-G is the most critical part on the study of the pathogenesis of HLA and pre-eclampsia.HLA-G gene polymorphism includs coding and non-coding region polymorphisms.The non-coding region polymorphisms of HLA-G including 5’-upstream regulatory region(5’-URR) and 3’-untranslated gegion(3’-UTR).This polymorphisms is the hot spots of the relationship between HLA-G gene polymorphism and pre-eclamps.The lasted reaserchs showed that the SNP3172 polymorphism of HLA-G 3’-UTR is relation to pre-eclamps,then reduced the stability of HLA-G mRNA.Other researchs consider the relationship between HLA-G 3’-UTR SNP3172 polymorphism and preeclamps from the aspect of newborn,showed that when the genotype of newborn is SNP2995(C)/SNP3127(G)/SNP3172(A)/SNP3181 (G)/+14bp homozygous,it has greater correlation with preeclamps.But it is not comprehensive that consider the HLA-G polymorphism and the relationship with pre-eclampsia,when many studies confirmed only from the baby or from the mother.The gestation may be the interaction of the mother’s and baby’ gene.And this polymorphism may be a result of geographic, racial and ethnic differences,and it is still need to study.ObjectiveHLA-G 3’-UTR genotyping was performed by polymerase chain reaction (PCR) in pre-eclampsia patients and normal pregnant women and their fetal, among October 2008 and November 2010 in the Third Affiliated Hospital of Zhengzhou University Hospital, in the Chinese Han population in Henan Province.Then respectively compareed the distributions of the genotype and allele frequencies frequencies of the two groups.Then to analyze the differences of the combine of maternal and fetal of the genotype special bindings.The research of the HLA-G polymorphism and the relationship with pre-eclampsia provide an important mechanism of clues of the pathogenesis of pre-eclampsia, and also provide experimental evidence for clinical information between the maternal-fetal morbidity predict the risk of pre-eclampsia.Materials and methods1 MaterialsChoose 53 pre-eclampsia patients,32 newborns and 27 pairs of pregnant women and their fetal,51 normal pregnant women,41 newborns and 35 pairs of normal pregnant women and their fetal,among October 2008 and November 2010 in the Third Affiliated Hospital of Zhengzhou University Hospital. The standard of diagnosis is according to the People’s Medical Publishing House on th 7rd edition of Obstetric and Gynecology, and excluding the chronic hypertension,kidney disease,inflammation,endocrine disease,diabetes and cancer etc.And all patients were followed up to 12 weeks after delivery. The two groups of pregnant women were residents of Henan Province, no history of mixed marriages, non-blood relations, and then compared the maternal age, gestational age, and parity, there was no significant difference (P>0.05).2 MethodsHLA-G 3’-UTR genotyping was performed by polymerase chain reaction (PCR) in pre-eclampsia patients and normal pregnant women and their fetal.3 Statistics analysisAll data using SS16.0 software package for statistics analysis.Judging whether the genotype distribution of Hardy-Weinberg equilibrium.Using the single-factor analysis of variance to measure the data between the two groups.Calulation the frequency of allelic genes directly,the distribution differences of allele frequency between the two groups usingχ2-test. n≥40 andT≥5, usingχ2-test; n≥40 but 1≤T<5 using continuous correction method to calculate P values; n<40 or T<1, using the Fisher exact probability method or,and in order to test the level of a=0.05.ResultsAnalysis the HLA-G gene 3’-UTR SNP polymorphism between pre-eclampsia group and the normal pregnant group,find that it is consistent with Hardy-Weinberg equilibrium(P>0.05).We found three polymorphisms on HLA-G gene 3’-UTR—locus 3127 (rs1063320) C→G、locus 3172 (rs9380142) G→A、locus 3181 (rs1610696) C→G。1 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP polymorphism between the mother group 1.1 The comparison of allele and genotype frequency of HLA-G gene 3’-UTRSNP3127 polymorphism between the mother groupIn our study,we detected G、C allele existed in the HLA-G gene 3’-UTR locus 3127,and CG、CC、GG genotypes.The allele frequencies of HLA-G 3’-UTR SNP3127 in pre-eclampsia:G is 47.2%,C is 52.8%.52.0%,48.0%。Compared the two groups,there is no significant difference(P>0.05).The CG allele frequencies in pre-eclampsia group is 45.3%,and it is lower than 64.7% of normal group,compared the two groups,the differences were statistically significant(P<0.05).1.2 The comparison of allele and genotype frequency of HLA-G gene 3’-UTRSNP3172 polymorphism between themother groupIn our study,we detected G、A allele existed in the HLA-G gene 3’-UTR locus 3172,and AA、AG、GG genotypes.The allele frequencies of HLA-G 3’-UTR SNP3172 in pre-eclampsia:G is 42.5%, A is 57.5%. The control group is 36.3%,63.7%.Compared the two groups,there is no significant difference(P >0.05).The AA allele frequencies in pre-eclampsia group is 50.9%,and it is higher than 25.5% of normal group,compared the two groups,the differences were statistically significant(P<0.05).1.3 The comparison of allele and genotype frequency of HLA-G gene 3’-UTRSNP3181 polymorphism between the mother groupIn our study,we detected G、C allele existed in the HLA-G gene 3’-UTR locus 3181,and CG、CC、GG genotypes.The allele frequencies of HLA-G 3’-UTR SNP3181 in pre-eclampsia:G is 33.0%,C is 67.0%. The control group is 36.3%,63.7%.Compared the two groups,there is no significant difference(P>0.05). Compared the genotype frequency distribution between the two groups, the differences were no statistically significant (P>0.05).2 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP3172 polymorphism between the newborn group2.1 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP3127 polymorphism between the newborn groupThe allele frequencies of HLA-G 3’-UTR SNP3127 in pre-eclampsia:G is 46.9%,C is 53.1%. The control group is 45.1%,54.9%. Compared the two groups,there is no significant difference(P>0.05). Compared the genotype frequency distribution between the two groups, the differences were no statistically significant (P>0.05).2.2 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP3172 polymorphism between the newborn groupThe allele frequencies of HLA-G 3’-UTR SNP3172 in pre-eclampsia:G is 45.3%,A is 54.7%. The control group is 43.9%,56.1%. Compared the two groups,there is no significant difference(.P>0.05). Compared the genotype frequency distribution between the two groups, the differences were no statistically significant (P>0.05).2.3 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP3181 polymorphism between the newborn groupThe allele frequencies of HLA-G 3’-UTR SNP3181 in pre-eclampsia:G is 20.7%,C is 57.3%. The control group is 34.1%,65.9%. Compared the two groups,there is no significant difference(P>0.05). Compared the genotype frequency distribution between the two groups, the differences were no statistically significant (P>0.05).3 The comparison of allele and genotype frequency of HLA-G gene 3’-UTR SNP3181 polymorphism between the two group3.1 The comparison of maternal/fetal HLA-G gene 3’-UTR SNP3127 polymorphism genotype compatibility between the two groupCompared theHLA-G gene 3’-UTR SNP3127 polymorphism genotype compatibility between the two groups,there is no signigicant difference(P>0.05).3.2 The comparison of maternal/fetal HLA-G gene 3’-UTR SNP3172 polymorphism genotype compatibility between the two groupIn pre-eclampsia group,the frequencies of maternal/fetal genotype AA/AA is 48.1%,it is higher than 31.4% of normal pregnant group,compared the two groups, the differences were statistically significant(P<0.05). 3.3 The comparison of maternal/fetal HLA-G gene 3’-UTR SNP3181 polymorphism genotype compatibility between the two groupIn pre-eclampsia group,the frequencies of maternal/fetal genotype CG/CG is 14.8%, it is higher than 40.0% of normal pregnant group,compared the two groups, the differences were statistically significant(P<0.05).Conclusions1. It suggested that HLA-G gent 3’-UTR 3127 locus SNP polymorphism may be the protection factor of pre-eclampsia,3172 SNP may relative to the susceptibility of Pre-eclampsia in Chinese Han population in Henan province.2. When the maternal/fetal HLA-G gene 3’-UTR 3181 SNP genotype is(CG/CG), the mather fall preeclampsia risk may happen to lower;when the maternal/fetal HLA-G gene 3’-UTR 3181 SNP genotype is(AA/AA), the mather fall preeclampsia risk may happen to higher.

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