胎龄≤34周的汉族早产儿脐带血内皮型一氧化氮合成酶基因多态性及其与早产儿主要并发症的关系研究

摘要

目的 探讨新乡市汉族早产儿脐带血内皮型一氧化氮合成酶(eNOS)基因的多态性,并研究这种多态性与早产儿主要并发症的关系.方法 选择2014年2月—2016年12月于新乡市中心医院出生的≤34周的早产儿231例为研究对象,母亲分娩时取脐带血,测定eNOS基因3个位点rs2070744、rs1799983和rs61722009的基因型和等位基因.记录早产儿的临床资料,分析eNOS基因多态性与早产儿主要并发症的关系.结果 rs2070744 C、rs1799983 T和rs61722009 a的等位基因频率分别是0.145、0.188和0.159.与Ensembl数据库中已知研究比较,差异无统计学意义(χ2=0.875,P=0.646;χ2=3.541,P=0.173).单因素分析结果示rs2070744 TC+CC基因型和rs1799983 GT+TT基因型与支气管肺发育不良有关(crude OR=0.370、0.484,P=0.003、0.030).多因素Logistic回归分析结果示rs2070744 TC+CC基因型是支气管肺发育不良的独立危险因素(OR=1.875,P=0.020);rs61722009 aa+ab基因型和rs1799983 GT+TT基因型同时存在是早产儿视网膜病变Ⅲ~Ⅴ期的独立危险因素(OR=2.961,P=0.041).结论 eNOS基因多态性与早产儿主要并发症的发生有关,脐带血测定早产儿eNOS基因多态性有助于评估患儿预后.%Objective To examine the association of gene polymorphisms of nitric oxide synthase(NOS) in endothelial cells of umbilical cord vessels and major complications among Han premature infants of ≤ 34 weeks' gestational age in Xinxiang.Methods This study was conducted in a cohort of preterm infants(n=231) with a gestational age of ≤ 34 weeks delivered in Xinxiang Central Hospital from February 2014 to December 2016.Allele and genotype frequencies at 3 single nucleotide polymorphism(s rs2070744,rs1799983 and rs61722009) of eNOS in endothelial cells of umbilical cord vessels(extracted at the delivery).We collected the clinical data of the preterm infants.The association of gene polymorphisms of eNOS with the development of bronchopulmonary dysplasia(BPD),necrotizing enterocolitis(NEC),stage Ⅲ-Ⅴ retinopathy(ROP), stage Ⅲ-Ⅳ periventricular-intraventricular hemorrhage(PIVH),neonatal respiratory distress syndrome(RDS) requiring mechanical ventilation(MV) and death.Results The frequency of C allele of rs2070744 polymorphism,and T allele of rs1799983 polymorphism was 0.145,0.188,respectively,which was similar to that proposed in the studies collected in Ensembl genome database(χ2=0.875,P=0.646;χ2=3.541,P=0.173).The a allele of rs61722009 polymorphism was identified to be 0.159.Univariate analysis found that rs2070744 TC+CC genotypes(crude OR=0.370,P=0.003) and rs1799983 GT+TT genotypes(crude OR=0.484,P=0.030) were associated with the development of BPD.Multivariate Logistic regression analysis revealed that rs2070744 TC+CC genotypes were independent risk factors for BPD(OR=1.875,P=0.020),and synchronized appearance of rs61722009 aa+ab and rs1799983 GT+TT genotypes were independent risk factors for stage Ⅲ-ⅤROP(OR=2.961,P=0.041).Conclusion The eNOS gene polymorphisms are associated with the major complications of Han preterm infants in Xinxiang.Genotyping may be helpful to identify patients with higher risk of BPD and stage Ⅲ-ⅤROP.