| Objectives:(1)To investigate associations between JAG1 gene polymorphism and preeclampsia in pregnant women;(2)To explore the association of the JAG1 gene haplotype and preeclampsia during pregnancy;(3)To explore the association of interactions between various SNP(Single Nucleotide Polymorphism,SNP)sites in the JAG1 gene and the occurrence of preeclampsia.Methods:This is a case control study based on the hospital.Pregnant women seeking medical advice from March to December 2021 in Obstetrics Department I and the Outpatient Department of Hunan Maternal and Child Health Hospital were selected;and they also meet relevant incorporation criteria.Through epidemiological questionnaire surveys,fundamental data of the participants and their spouses were collected,and then recorded and analyzed by software Epidata 3.0 and SPSS 25.0.Moreover,JAG1 gene’s 12 genetic loci to be detected were tested.While Chi-square tests and Fisher’s exact tests were conducted to carry out univariate analysis,multivariate analyses were performed by logistic regression analysis.In this way,associations of JAG1 gene polymorphism with pre0eclampsia were studied for these participants.Additionally,Haploview 4.2 was further adopted to detect linkage disequilibrium of various JAG1 gene’s SNPs,construct haplotypes,and evaluate the relationship between each haplotype and the development of preeclampsia.Finally,associations between the interaction of JAG1gene’s SNPs and preeclampsia were assessed by virtue of the software GMDR 0.9.Results:Eventually,383 participants are included in this study.Among them,117 pregnant women diagnosed with preeclampsia form a case group;and 266 who are not diagnosed with preeclampsia in the corresponding period constitute the control group.(1)It turns out that PE development risks during pregnancy are associated with recessive model of genetic locus rs1051412(CC vs AA+AC:OR=0.47,95%CI:0.27-0.83),as well as codominant genetic model(CG vs CC:OR=0.56,95%CI:0.34-0.92),dominant genetic model(CG+GG vs CC:OR=0.54,95%CI:0.33-0.86),overdominance model(CG vs CC+GG:OR=0.60,95%CI:0.37-0.97)and additive genetic model(GG vs CC\CG:OR=0.58,95%CI:0.38-0.87)of the locus rs73604319.(2)According to haplotype analysis results,differences in the frequencydistributionofhaplotypes CTCG(χ~2=3.854,P=0.047;OR=0.65,95%CI:0.43-0.99)and CCCG(χ~2=5.032,P=0.025;OR=0.56,95%CI:0.34-0.92)produced by intragenic loci rs1051412-rs73611723-rs7264849-rs73604319 are of statistical significance between case and control groups.Moreover,they may be associated with the reduction in preeclampsia development risks.(3)As indicated in generalized multifactor dimensionality reduction-based analysis results,first-order interaction of SNPs in JAG1gene serves as the optimum model,involving rs73604319 and rs73611723 and producing the highest accuracy(0.5504)and cross validation consistency(8/10)among the tested samples(P=0.0004).Based on the first-order interaction,it is demonstrated by multivariate logistic regression results that those pregnant women carrying CG or GG genotype at the locus rs73604319,and CT or TT genotype of locus rs73611723 show significantly lowered preeclampsia development risks in comparison with those with CC genotypes of loci rs73604319 and rs73611723(OR=0.55,95%CI:0.32-0.93;P=0.025).Conclusions:First,loci rs1051412、rs73604319 in JAG1 genes are associated with preeclampsia according to the corresponding genetic model.Concerning the loci rs1051412 A→C(recessive model)and the loci rs73604319C→G(i.e.,the codominant genetic model,the dominant genetic model,the overdominance genetic model and the additive genetic model),both loci development risks of preeclampsia are significantly reduced.Second,the reason why JAG1 gene’s SNP of pregnant women forms two haplotypes(rs1051412-rs73611723-rs7264849-rs73604319:CTCG and CCCG)may be related to the development of preeclampsia in them and the drop of preeclampsia development risks.At last,among JAG1 gene’s SNPs during pregnancy,the interaction between loci rs73604319 and rs73611723 is the optimum model.In combination with relevant logistic regression analysis results,it can be pointed out that the preeclampsia development risk can be markedly lowered in pregnant women possessing CG or GG phenotype at the locus rs73604319 and CT or TT genotype at the locus rs73611723. |
