The Effects Of Maternal And Fetal KDR Gene Single Nucleotide Polymorphisms On Pre-eclampsia

Objectives:1.To investigate the risk factors leading to pre-eclampsia（demographic characteristics,family history,pregnancy-related information,daily life behaviors,mental condition）.2.To explore the association between maternal and fetal KDR single nucleotide polymorphisms（SNPs）and pre-eclampsia.3.To investigate the gene-environment interactions between maternal KDR SNPs and risk factors.Methods:1.The study subjects（203 pre-eclampsia patients with their husbands and baby,318 normotensive controls with their babies）were selected from two Maternal and Child Care Hospitals in Anyang and Yichang city（in Henan and Hubei province respectively）from January 2008 to October 2015.A well-designed questionnaire consisting of five aspects（demographic characteristics,family history,information about pregnancy,lifestyle,mental condition）was used to collect the subjects’ information.2.The targeted sequencing of KDR gene was conducted in the case-control study including 50 pre-eclampsia pregnancies and normotensive controls with their babies.The target SNPs were selected based on results of association analysis between KDR SNPs and pre-eclampsia.The Taq Man^TM SNP Genotyping was used to genotype these blood samples.3.Goodness-of-fit χ2 test was used for evaluating the HWE for all genotypes.The Pearson’s χ2 test was used to analyzed differences of allelic and genotype frequency in the patients and the controls.The relationship between maternal and fetal genotypes and pre-eclampsia under different genetic models,including dominant,recessive,additive and co-dominant,were evaluated by the unconditional logistic regression.In the caseparents/control-mother design,a log-linear model was employed to explored the maternal and fetal KDR SNPs in pre-eclampsia.4.The software of Phase2.1 was employed to build maternal and fetal KDR haplotypes.The unconditional logistic regression was employed to explore the influence of haplotypes on pre-eclampsia.5.The multivariate logistic regression method was employed to analyze the risk factors associated with pre-eclampsia were selected.Then,log-linear model was employed to investigate the gene-risk factors interactions.Results:1.Three SNPs（rs1870377,rs2305948,rs7667298）were selected in the current study.For maternal and fetal rs2305948,there were significant differences in the distribution of genotypes in both cases and controls.In the genetic model analysis,maternal and fetal rs2305948 in the dominant,recessive and additive model（maternal:OR=2.98,95%CI:1.28-6.95;OR=1.61,95%CI:1.10-2.37;OR=3.32,95%CI:1.41-7.82,fetal:OR=2.52,95%CI:1.23-5.16;OR=1.74,95%CI:1.18-2.57;OR=2.89,95%CI:1.39-6.01）were significantly associated with increased risk of pre-eclampsia.In the loglinear model analysis,maternal TT genotype compared to CC genotype could increase the risk of pre-eclampsia（OR=1.88,95%CI:1.27-2.79）.No association was observed between other SNPs（rs1870377 and rs7667298）and pre-eclampsia.2.In the haplotype analysis,compared with TCC haplotype（rs1870377-rs2305948-rs7667298）,mother carrying ACC and ACT haplotype（OR=2.32,95%CI: 1.60-3.37;OR=1.46,95%CI:1.01-2.14）and fetus carrying ACC haplotype（OR=2.68,95%CI:1.86-3.87）increased the risk of pre-eclampsia,whereas,mother with TCT haplotype could decrease the risk of pre-eclampsia（OR=0.33,95%CI:0.15-0.76）.3.In the gene-risk factors interaction analysis,maternal rs1870377 had a significant interaction with passive smoking.In the passive smoking group,maternal rs1870377 TT genotype compared with AA genotype was associated with the decreased risk of preeclampsia（OR=0.27,95%CI:0.11-0.68,p=0.005）.Conclusions:1.For the rs2305948,maternal and fetal additive model,dominant model and recessive model would increase the risk of pre-eclampsia.In the hybrid design analysis,maternal rs2305948 TT genotype was associated with the increased risk of preeclampsia.2.Maternal ACC and ACT haplotype and fetal ACC haplotype increased the risk of pre-eclampsia.Whereas,maternal TCT haplotype was associated with decreased risk of pre-eclampsia.3.Maternal rs1870377 had an interaction with passive smoking,and significantly association was observed between maternal AA genotype and passive smoking.