| Objectives:The purpose of this thesis is to investigate the relationship of maternal blood glucose levels during pregnancy and neonatal hyperinsulinemia and cardiac abnormalities.By testing the genetic polymorphism of GATA-4,the correlation between GATA-4 gene polymorphism and abnormal heart development in infants of diabetic mothers is analyzed.Methods:1.This study has collected 69 full term babies with Infants of Diabetes Mothers in Neonatal care unit in the first afiliated hospital of Kunming medical university from September,2018 to April,2019.Micro-glucose of blood were tested at admission.In the early morning of next day,and we also tested synchronous micro blood glucose and serum insulin.Besides,Cardiac ultrasound was completed.2.69 IDMs were divided into groups:① According to the diagnostic criteria of hyperinsulinemia,the patients were divided into two groups:the hyperinsulinemia group and the non-hyperinsulinemia group.The incidence of cardiac dysplasia was compared between the two groups.②According to the blood glucose levels during pregnancy of GDM mothers,the children were divided into two group:good blood glucose levels and the group with poor blood glucose levels.The incidence of cardiac dysplasia was compared between the two groups.3.18 cases of IDMs with cardiac abnormalities and 2 cases of IDMs with normal heart development were selected,and their GATA4 gene polymorphism were tested.The genotypes of mutation mode sequence of each polymorphic locus were analyzed.Also,they were divided into groups:① According to the degree of cardiac abnormalities,divided into the multiple abnormal heart development group and the single abnormal heart development group.The distribution of genotypes and gene frequencies corresponding to gene polymorphism between two groups was studied.② According to the level of insulin,the IDMs were divided into two groups:the hyperinsulinemia group and the non-hyperinsulinemia group.The distribution of genotypes and gene frequencies corresponding to gene polymorphism between two groups was studied.③ According to the maternal blood glucose levels during pregnancy,the IDMs were divided into the good blood glucose control group and the poor blood glucose control group.The distribution of genotypes and gene frequencies corresponding to gene polymorphism between two groups was studied.Results:1.General analysis on IDMs:By cardiac ultrasound,it was found that 26 cases(37.68%)had abnormal heart development.Types of IDMs heart included:patent dutcus arterious 15 cases(17.39%),atrial spetal defect 8 cases(11.59%),ventricular septal defect 3 cases(4.35%),pulmonary hypertension 2 cases(2.90%),atrial septal aneurysm 2 cases(2.90%),myocardial hypertrophy 2 cases(2.90%)and 1 case(1.45%)of double-chamber right ventricle.2.Heart development were observed between groups:① Among the 13 IDMs in the hyperinsulinemia group,46.2%of the hyperinsulinemia had abnormal heart development.In the non hyperinsulinemia group(56 cases),35.7%of the non hyperinsulinemia had abnormal heart development,P>0.05,which was no statistical significance.②In the group with poor blood glucose control(11 cases),72.7%of the poor blood glucose control had abnormal heart development.In the good control group(58 cases),31.0%had abnormal heart development,In the group with poor blood glucose control,the incidence of abnormal heart development was significantly higher than that in the group with good blood glucose control,and the heart development was compared between the two groups,P<0.05,which was statistically significant.3.Polymorphism of GATA-4 gene of IDMs and GATA-4 alleles of genotype and allele results:the GATA4 genetic polymorphisms for 20 cases of IDMs were tested.We tested the exon 1-7 exons,and found a total of 9 SNP polymorphism loci(rs573733348、rs201533584、rs804280、rs867858、rs78334561、rs884662、rs904018、rs12825、rs804291).The gene frequency of all polymorphic loci with mutations were calculated.The frequencies of rs573733348、rs201533584、rs867858、rs884662、rs804291 are 2.5%,2.5%,100%,17.5%,100%,respectively,which were all higher than of 1.6%,0.1%,98.1%,16.9%,99.9%in the genetic library of Asian area.The rest were lower.The incidence of gene frequenc were compared between the two groups,P>0.05,which was no statistical significance.① The analysis of GATA-4 gene polymorphism and heart abnormality of IDMs:The genotypes and gene frequencies corresponding to each polymorphic locus were compared in different degrees of cardiac abnormalities:rs904018(TC/CC),P=0.220.rs867858(AC/CC/AA),P=0.143.rs884662(TC/TT),P=0.515.rs12825(CG/GG/CC),P=0.118.P>0.05,which was not statistically significant.Genetic frequencies were compared between the two groups:rs904018(T.C),P=0.285.rs867858(A.C),P=0.311.rs884662(C.T),P=0.510.rsl2825(C.G),P=0.311.P>0.05,which were no statistical significance.②Correlation analysis between GATA-4 polymorphism and insulin level:The distribution of the genetic frequency corresponding to the polymorphic locus rs867858.rs904018.rs884662.rs12825 in the hyperinsulinemia group and the non-hyperinsulinemia group are statistically analyzed:rs904018(T.C)were compared between the two groups,P=0.337.rs867858(A.C)were compared between the two groups,P=0.292.rs884662(C.T)were compared between the two groups,P=0.526.rs12825(C.G)were compared between the two groups,P=0.292.rs904018 corresponding genotype frequency were compared between the two groups,P=0.693.P>0.05,which were no statistical significance.?Correlation analysis between GATA-4 polymorphism and maternal glucose control during pregnancy:The distribution of the genetic frequency corresponding to the polymorphic locus rs867858,rs904018,rs884662,rsl2825 in the group with poor blood glucose control during pregnancy and the group with good blood glucose control were statistically analyzed;rs904018(T.C)were compared between the two groups,P=0.337.rs867858(A.C)were compared between the two groups,P=0.429.rs12825(C.G)were compared between the two groups,P=0.429.and the genotype frequency corresponding to rs904018 were compared between the two groups:P=0.307.P>0.05,which were no statistical significance.Conclusions:1 Good control of blood glucose of diabetic mother during pregnant could reduce the incidence of abnormal heart development in IDMs.2 The GATA-4 gene polymorphism locus associated with congenital heart disease could be tested in infants of diabetic mothers with cardiac abnormalities.3 There is no significant difference between the degree of cardiac dysplasia and GATA-4 polymorphism.Similarly,There is no significant in maternal glucose levels and the levels of insulin in infant of diabetic mothers with GATA-4 polymorphism. |
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