孕妇及其子代ERAP-1基因多态性与子痫前期发生的相关性

Relationship between maternal and fetal ERAP-1 gene polymorphism and pre-eclampsia

目的:探讨孕妇及其子代内质网氨基肽酶1(ERAP-1)基因多态性与子痫前期(PE)发生的相关性。方法:采用病例对照研究方法,选择2018年10月至2021年10月于首都医科大学附属北京妇产医院住院分娩、发病孕周<34周的PE孕妇51例作为观察对象(PE组),选择同期正常分娩孕妇48例作为对照组。采集孕妇分娩前的静脉血和胎儿娩出后5 min内的脐血,采用二代测序技术检测孕妇及其子代ERAP-1基因的单核苷酸多态性(SNP)位点。使用单因素分析和多因素logistic回归分析对两组所有检测的SNP位点及基因型进行分析,筛选有意义的SNP位点及基因型。结果:(1)单因素分析筛选出孕妇ERAP-1基因的目的SNP位点共计13个,其中,96096828、96121524、96121715、96122260、96122281位点的基因型分布在PE组与对照组之间的差异均有统计学意义(P均<0.05)。多因素logistic回归分析结果显示,96121524位点基因型为TC的孕妇发生PE的风险是基因型为TT孕妇的2.002倍(95%CI为0.687~5.831,P=0.020)。(2)单因素分析筛选出子代ERAP-1基因的目的SNP位点共4个,4个位点的基因分布在PE组与对照组之间的差异均无统计学意义(P均>0.05)。多因素logistic回归分析结果显示,96121406位点基因型为AA的子代发生PE的风险是基因型为GG子代的0.236倍(95%CI为0.055~1.025,P=0.016)。结论:ERAP-1基因在孕妇96121524位点基因型为TC、在子代96121406位点基因型为GG可能是PE发生的影响因素。

Objective To investigate the relationship between the polymorphism of endoplasmic reticulum aminopeptidase 1(ERAP-1)gene and the occurrence of pre-eclampsia(PE).Methods A case-control study was conducted in Beijing Obstetrics and Gynecology Hospital from October 2018 to October 2021.A total of 51 PE pregnant women with onset gestational age<34 weeks were selected as the PE group,and 48 normal pregnant women during the same period were selected as the control group.Venous blood samples were collected from the pregnant women before delivery and umbilical cord within 5 minutes after delivery.Single nucleotide polymorphisms(SNP)of ERAP-1 gene in the pregnant women and their fetus were detected by next-generation sequencing.Univariate analysis and multivariate logistic regression analysis were used to analyze all the SNP loci and alleles detected in the two groups,and the significant SNP were screened.Results(1)A total of 13 target SNP loci of maternal ERAP-1 gene were selected by univariate analysis.Among them,the frequency distribution of genotypes at 96096828,96121524,96121715,96122260 and 96122281 showed statistically significant differences between PE group and control group(all P<0.05).Multivariate logistic regression analysis showed that the risk of PE in pregnant women with TC genotype at locus 96121524 was 2.002 times higher than those with TT genotype(95%CI:0.687-5.831,P=0.020).(2)A total of 4 target SNP loci of ERAP-1 gene in fetal were selected by univariate analysis,and there was no statistical significance in gene polymorphism of the 4 loci between PE group and control group(all P>0.05).Multivariate logistic regression analysis showed that the risk of PE in fetus with genotype AA at locus 96121406 was 0.236 times that of fetus with genotype GG(95%CI:0.055-1.025,P=0.016).Conclusion ERAP-1 gene with TC genotype at 96121524 in the mother and GG genotype at 96121406 in the fetus might be related to the incidence of PE.