细胞周期蛋白D1和细胞周期蛋白E1基因多态性及其交互作用与先兆子痫的关联研究  

Study on the Association between Polymorphisms and Interaction of CCND1 and CCNE1 Genes with Preeclampsia

作　　者：周韵哲 苗竣翔 韦杰桦 陈立章 王婷婷 ZHOU Yunzhe;MIAO Junxiang;WEI Jiehua;CHEN Lizhang;WANG Tingting(Department of Epidemiology and Health Statistics,Xiangya School of Public Health,Central South University,Changsha 410078,China)

机构地区：[1]中南大学湘雅公共卫生学院流行病与卫生统计系,湖南省长沙市410078

出　　处：《中国全科医学》2025年第17期2142-2148,共7页Chinese General Practice

基　　金：国家自然科学基金资助项目(82173608)。

摘　　要：背景先兆子痫(PE)是一种致命的多系统疾病,严重威胁妇女和胎儿的健康。目的探索细胞周期蛋白D1(CCND1)和细胞周期蛋白E1(CCNE1)基因多态性及其交互作用与PE的关联,为PE病因学研究提供科学依据。方法采用病例对照研究设计,招募2020年10月—2023年10月在中南大学湘雅三医院和湖南省妇幼保健院产科就诊的202例PE患者作为病例组,以同期在该院产检且血压正常的400例孕产妇作为对照组。采用多因素Logistic回归分析探讨CCND1和CCNE1基因多态性与PE发生的关联,并计算调整后比值比(aOR)及95%置信区间(95%CI)。采用叉生分析探索基因-基因相加交互作用与PE的关联。使用3DSNP数据库对单核苷酸多态性(SNP)位点进行功能注释。结果多因素Logistic回归分析发现,CCND1 rs1352075位点携带CT/TT基因型孕妇发生PE的风险低于CC基因型(显性模型:aOR=0.44,95%CI=0.20~0.96,P<0.05)。CCNE1 rs3218070位点携带GG基因型孕妇发生PE的风险高于CC/GC基因型(隐性模型:aOR=4.31,95%CI=1.16~16.04,P<0.05)。3DSNP数据库分析结果显示rs1352075和rs3218070染色质开放区域中,与血管以及胎盘形成相关的细胞调控因子结合位点占比较高。交互作用分析显示,rs1352075和rs3218070位点间的相加交互作用与PE发生无关。结论CCND1 rs1352075位点携带CC基因型和CCNE1 rs3218070位点携带GG基因型可能与PE发生风险升高有关。Background Preeclampsia(PE)is a life-threatening multisystemic disorder that significantly endangers maternal and fetal health.Objective To investigate the association between CCND1(Cyclin D1)and CCNE1(Cyclin E1)gene polymorphisms,as well as their interactions with the risk of PE,and provide scientific evidence for its pathogenesis.Methods A case-control study was conducted.From October 2020 to October 2023,pregnant women diagnosed with PE were recruited from the Xiangya Third Hospital of Central South University and the Hunan Provincial Maternal and Child Health Hospital as the case group(n=202),while pregnant women with normal blood pressure were recruited as the control group(n=400).Multivariate Logistic regression analyses were performed to evaluate the association between CCND1 and CCNE1 gene polymorphisms and the risk of PE,with adjusted odds ratios(aOR)and 95%confidence intervals(95%CI)calculated.Interaction analysis was performed to investigate the association between gene-gene interactions and PE risk.Functional annotation of single nucleotide polymorphisms(SNP)was performed using the 3DSNP database.Results Multivariate Logistic regression analysis revealed that pregnant women with the CT/TT genotype at CCND1 rs1352075 had a lower risk of PE compared to CC genotype(dominant model:aOR=0.44,95%CI=0.20-0.96).Pregnant women with the GG genotype at CCNE1 rs3218070 had a higher risk of PE compared to CC/GC genotype(recessive model:aOR=4.31,95%CI=1.16-16.04).Analysis based on the 3DSNP database revealed a higher proportion of cellular regulatory factors related to vascularization and placentation in the open chromatin regions at rs1352075 and rs3218070 binding sites.Interaction analysis showed that the additive interaction between rs1352075 and rs3218070 was not significantly associated with PE risk.Conclusion The CCND1 rs1352075 locus harboring the CC genotype and the CCNE1 rs3218070 locus harboring the GG genotype may be associated with an elevated risk of developing PE.

关 键 词：先兆子痫 细胞周期蛋白D1 细胞周期蛋白E1 单核苷酸基因多态性 病例对照研究 LOGISTIC回归分析 

分 类 号：R714.244[医药卫生—妇产科学]