FCN基因单核苷酸多态性对汉族孕妇子痫前期易感性的影响

Effect of FCN gene single nucleotide polymorphism on the susceptibility of pre-eclampsia in Han nationality pregnant women

目的探讨FCN基因的单核苷酸多态性(SNP)对汉族孕妇子痫前期(PE)易感性的影响。方法收集2020年10月至2022年10月南方医科大学附属中山市博爱医院收治的PE孕妇274例(PE组)和同期收治的健康孕妇154例(对照组),比较两组孕妇的一般资料、既往史、生育史、血压、体重指数和临产前血生化指标。采用飞行时间质谱检测系统对FCN基因家族的23个SNP位点进行基因分型,并用酶联免疫吸附试验检测其编码产物纤维胶凝蛋白(ficolin,包括ficolin-1、ficolin-2和ficolin-3)的血清水平。结果(1)与对照组比较,PE组孕妇的体重指数、平均动脉压、分娩孕周、血尿素氮、丙氨酸转氨酶、天冬氨酸转氨酶、直接胆红素、白蛋白、C反应蛋白、氨基末端脑利钠肽前体(NT-proBNP)、胎盘生长因子(PlGF)和人可溶性血管内皮生长因子受体1(sFlt-1)水平均有显著差异(P均<0.05)。(2)FCN基因的23个SNP位点中,18个位点符合Hardy-Weinberg遗传平衡定律,包括FCN1基因5个位点、FCN2基因10个位点、FCN3基因3个位点;不符合Hardy-Weinberg遗传平衡定律的5个位点不纳入后续分析。与对照组比较,PE组FCN2基因的3个位点(rs7872508、rs11103563、rs73664188)和FCN3基因的1个位点(rs3813800)的基因型分布有显著差异(P均<0.05)。经Bonferroni校正,仅FCN2基因的rs7872508和rs73664188两个SNP位点的基因型分布在PE组与对照组孕妇中的差异有统计学意义(P均<0.05)。进一步分析显示,对于FCN2基因的rs7872508位点,与GG基因型比较,基因型为GT(OR=3.025,95%CI为1.080~8.471)和TT(OR=4.777,95%CI为1.758~12.979)均显著增加PE的发生风险(P均<0.05)。对于FCN2基因的rs73664188位点,与TT基因型比较,基因型为TC(OR=0.510,95%CI为0.334~0.778)显著降低PE的发生风险(P<0.05)。(3)与对照组相比,PE组孕妇血清ficolin-1和ficolin-2水平均显著降低(P均<0.05),ficolin-3水平则无显著变化(P=0.271)。相关性分析显示,PE组孕妇血清ficolin-2水平与PlGF水平呈显著正相关(r=0.321,P<0.001),与sFlt-1(r=-0.187,P=0.002)和NT-proBNP(r=-0.392,P<0.001)水平呈显著负相关。进一步分析发现,FCN2基因的rs7872508位点基因型为GT和TT的PE组孕妇血清ficolin-2水平显著降低(P均<0.05),rs73664188位点基因型为TC的PE组孕妇血清ficolin-2水平显著升高(P<0.05)。结论FCN基因家族中FCN2基因的SNP可能与PE的易感性有关,并对PE孕妇血清ficolin-2水平有影响。

Objective To investigate the effect of single nucleotide polymorphism(SNP)of FCN gene on the susceptibility of pre-eclampsia(PE)in Han nationality pregnant women.Methods A total of 274 PE pregnant women(PE group)and 154 healthy pregnant women(control group)admitted to Boai Hospital of Zhongshan,Affiliated Hospital to Southern Medical University from October 2020 to October 2022 were collected.The general information,medical history,reproductive history,blood pressure,body mass index and blood biochemical indicators before delivery were compared between the two groups.Twenty-three SNP loci of FCN gene family were genotyped by time-of-flight mass spectrometry,and the serum levels of ficolins(ficolin-1,-2 and-3)were detected by enzyme-linked immunosorbent assay.Results(1)Compared with the control group,the body mass index,mean arterial pressure,gestational age at delivery,blood urea nitrogen,alanine aminotransferase,aspartate aminotransferase,direct bilirubin,albumin,and C-reactive protein in the PE group were significantly higher than those in the control group(all P<0.05).The levels of N-terminal pro-B type natriuretic peptide(NT-proBNP),placental growth factor(PlGF)and human soluble vascular endothelial growth factor receptor-1(sFlt-1)were significantly different between the two groups(all P<0.05).(2)Among the 23 SNP loci in FCN gene family,18 loci were in Hardy-Weinberg genetic equilibrium,including 5 loci in FCN1 gene,10 loci in FCN2 gene,and 3 loci in FCN3 gene.Five loci that did not conform to Hardy-Weinberg genetic equilibrium were not included in the subsequent analysis.Compared with the control group,the genotype distribution of 3 loci of FCN2 gene(rs7872508,rs11103563,rs73664188)and 1 locus of FCN3 gene(rs3813800)in the PE group were significantly different(all P<0.05).After Bonferroni correction,only the genotype distribution of rs7872508 and rs73664188 in FCN2 gene were statistically different between the PE group and the control group(all P<0.05).Further analysis showed that for the rs7872508 locus of FCN2 gene,compared with GG genotype,genotype GT(OR=3.025,95%CI:1.080-8.471)and TT(OR=4.777,95%CI:1.758-12.979)both significantly increased the risk of PE(both P<0.05).For rs73664188 locus of FCN2 gene,compared with TT genotype,genotype TC(OR=0.510,95%CI:0.334-0.778)significantly reduced the risk of PE(P<0.05).(3)Compared with the control group,the serum levels of ficolin-1 and ficolin-2 in pregnant women in the PE group were significantly reduced(both P<0.05),while the level of ficolin-3 showed no significant change(P=0.271).Correlation analysis showed that the serum levels of ficolin-2 in pregnant women in the PE group were significantly positively correlated with PlGF level(r=0.321,P<0.001),and significantly negatively correlated with sFlt-1 level(r=-0.187,P=0.002)and NT-proBNP level(r=-0.392,P<0.001).Further analysis revealed that the serum levels of ficolin-2 in pregnant women of the PE group with GT and TT genotypes at rs7872508 locus of FCN2 gene were significantly reduced(both P<0.05),while the serum level of ficolin-2 in pregnant women of the PE group with TC genotype at the rs73664188 locus were significantly increased(P<0.05).Conclusion The SNP of FCN2 gene in FCN gene family might be related to the susceptibility to PE and have an effect on serum ficolin-2 level in PE pregnant women.