Association Between Pregnancy Induced Hypertension Syndrome And Gene Polymorphism Of MiRNAs Synthesis Pathway

Objective:Pregnancy induced hypertension（PIH）occurs during pregnancy and includes two subtypes:gestational hypertension（GH）and preeclampsia（PE）,which can contribute to infant development and maternal health adverse effects,environmental and genetic factors are jointly involved in the occurrence of PIH,but the specific pathogenesis is still unclear.Studies have found that PIH is abnormally related to micro RNAs（micro RNAs,mi RNAs）,and the expression level of mi RNAs is affected by the genetic polymorphisms in their synthesis pathways.We speculate that the single nucleotide polymorphisms（SNPs）of mi RNAs synthesis pathways are related to PIH.Susceptibility is related,but related research is lacking.Therefore,this study intends to conduct a case-control study in the Han population to explore the effects of gene polymorphisms in mi RNAs synthesis pathways on PIH.Method:From January 2012 to December 2014,a total of 222 PIH（pregnancy induced hypertension）patients（including 143 PE patients and79 GH patients）and 330 healthy pregnant women were recruited in this study.Carry out a case-control study.After the subjects signed the informed consent,their peripheral blood and clinical information were collected.The Sequenom Mass ARRAY process was used to genotype 9SNPs of 4 mi RNAs synthesis pathway genes DICER1（rs3742330,rs1057035 and rs13078）,DROSHA（rs17409893 and rs642321）,RAN（rs3803012 and rs14035）and XPO5（rs1106841 and rs2257082）.Chi-square test and analysis of variance were used to compare the differences in age,gestational age,previous delivery,smoking during pregnancy,the prevalence of gestational diabetes and the distribution of fetal gender in the case group and the control group.Using multivariate logistic regression to control age,gestational age,previous delivery,smoking during pregnancy,gestational diabetes,and fetal sex,the allele types,genotypes and PIH,PE,and GH of the above 9 SNP loci were estimated separately Associated,the results were explained using adjusted OR（odds ratio）value and 95%confidence interval（95%confidence interval,95%CI）,and multiple test correction method（FDR）was used to correct the P value.Results:1.A total of 522 subjects were included in this study,including330 in the control group and 222 in the case group（79 in the GH group and 143 in the PE group）.The average age of the control group was（27.98±3.82）years,the average age of the GH group was（29.26±5.41）years,and the average age of the PE group was（29.36±5.73）.The average age of the GH and PE groups was higher than that of the control group（P=0.004）;The average gestational week of the group was（39.35±2.97）weeks,the average gestational week of the GH group was（38.56±1.64）weeks,and the average gestational week of the PE group was（37.20±3.29）weeks.The average gestational week of the control group was higher than that of the GH group and the PE group（P<0.001）;the number of people suffering from GDM in the GH group and the PE group was higher than the number of people suffering from GDM in the control group（P<0.001）;there was no statistical difference between the control group and the GH group or the PE group in terms of parity,fetal sex,and active or passive smoking Academic significance（P>0.05）.2.Two allele types were detected at DICER1 rs1057065 and rs3742330respectively.The association of PIH,GH and PE with rs1057065 or rs3742330 locus allele polymorphism and locus genotype was not statistically significant（P>0.05）.DICER1 rs13078 detected both T and A bases.The probability of carrying T bases in GH patients was higher than that of normal women,and the difference was statistically significant（P=0.002）.After adjusting for age,gestational age at delivery,parity,active or passive smoking during pregnancy,GDM,and fetal sex,the DICER1 rs13078 TT genotype was still significantly associated with increased susceptibility to GH(OR_adj=3.17（95%CI:1.55,6.48）),P=0.009).Two alleles were detected at DROSHA rs17409893 and rs64232.There was no statistically significant association between PIH,GH,and PE with rs17409893 and rs64232 allele polymorphisms and locus genotype types（P>0.05）.RAN rs14035 site detected two bases,C and T,PIH,GH,PE and rs14035 allele polymorphisms and locus genotypes were not statistically significant（P>0.05）.RAN rs3803012 site detected two types of bases A and G and two genotypes of AA and AG.PIH,PE and rs3803012 alleles are more likely to carry A bases,and the difference is statistically significant.Allele types P are 0.023 and 0.009,respectively.After adjusting for confounding factors for PE,compared with AG genotype,RAN rs3803012 genotype increased the risk of PE for AA(OR_adj=2.15（95%CI:1.26,3.66）,P=0.045).XPO5 gene rs1106841 locus,two types of bases A and C were detected.GH is associated with rs1106841 allele polymorphism,and the association is statistically significant（P=0.019）,while PIH and PE are more common with this locus.There was no statistically significant association between morphology（P>0.05）.After adjusting for confounding,there was no statistically significant association between rs1106841 genotype and PIH,GH and PE（P>0.05）.Two alleles of T and C were detected at the rs2257082 locus of the XPO5 gene,PIH,GH and PE and rs2257082There was no statistically significant association between locus polymorphism and genotype type（P>0.05）.3.DICER1 rs1057035/rs13078/rs3742330 haplotype T-A-A and DORSHA rs17409893/rs642321 haplotype A-T are both associated with increased risk of GH,with OR of 2.75（95%CI:1.40,5.38）（P=0.008）and1.60（95%CI:1.12,2.29）（P=0.032）.RAN rs14035/rs3803012 haplotype C-G is associated with PE susceptibility,OR=2.08（95%CI:1.19,3.62）（P=0.024）;haplotype C-A is a protective factor for PE,OR=0.68（95%CI:0.50,0.93）（P=0.0.024）.Conclusion:The polymorphisms of mi RNAs synthesis pathway genes are related to the susceptibility to pregnancy-induced hypertension.Among them,the DICER1 rs1078 polymorphism is related to GH,and the RAN rs3803012 polymorphism is related to PE.