肺表面活性物质蛋白B基因多态性与新生儿呼吸窘迫综合征易感性的研究

摘要

目的 探讨肺泡表面活性物质蛋白B(SPB)基因多态性与新生儿呼吸窘迫综合征易感性的关系.方法 收集华中科技大学同济医学院附属同济医院的新生儿呼吸窘迫综合征(NRDS)诊断病例为病例组,并按1∶ 2比例收集胎龄和出生体重相匹配的无明显感染症状早产儿为对照组.应用聚合酶链反应-限制性片段长度多态(PCR-RFLP)分析技术及基因测序技术检测SPB-18A/C及SPB1580C/T多态性,观察两组间基因型频率和等位基因频率的差异.并复习文献比较本研究汉族与其他种族人群等位基因频率的差异.结果 2008至2010年NRDS组91例,对照组182名进入分析.①SPB-18A/C基因在NRDS组AA,AC,CC基因型频率分别为11.0%、40.7%和48.4%,对照组分别为6.6%、31.3%和62.1%;两组基因型频率差异无统计学意义(P>0.05);NRDS组A等位基因频率显著高于对照组(31.3% vs 22.3%).②SPB1580C/T基因在NRDS组TT、TC和CC基因型频率分别为5.5%、63.7%和45.1%,对照组分别为30.8%、6.6%和48.4%;两组基因型频率差异无统计学意义(P>0.05);NRDS组C等位基因频率显著高于对照组(79.1% vs 70.9%).③本研究汉族人、美国人、巴西人和丹麦人SPB1580等位基因C频率分别为79%、35%、41%和46%,差异有统计学意义(P<0.05),与日本人群等位基因C频率(72%)差异无统计学意义(P>0.05);本研究汉族人、巴西人、美国人和丹麦人SPB-18等位基因A频率分别为31%、58%、57%和61%,差异有统计学意义(P<0.05).结论本研究汉族人群SPB-18A/C及SPB1580C/T基因多态性是NRDS的危险因素.不同种族人群SPB1580C/T和SPB-18A/C基因多态性分布存在明显差异.%Objective To study the relationship between gene polymorphisms of surfactant protein B ( SPB ) and neonatal respiratory distress symdrome susceptibility.Methods Children diagnosed as neonatal respiratory distress syndrome( NRDS ) from Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology were enrolled.The children born at the same gestation age were taken as control group and the ratio of NRDS group to control group was 1: 2.Genomic DNA was extracted from peripheral blood by EDTA anticoagulation, using a standard Phenol/chloroform extraction procedure.The genetic polymorphisms of SPB-I8A/C and SPB1580C/T were analyzed with polymerase chain reaction restriction fragment length polymorphism( PCR-RFLP ) using the restriction enzyme Apapl and Dde Ⅰ.Statistical analyses were carried out using SPSS software version 13.0.The Hardy-weinberg equilibrium was determined for both NRDS and control groups.X2 test was used to detect the difference between two groups.Results Ninety one children with NDRS were chosen as NRDS group and 182 children were enrolled as control group from 2008 to 2010.①The SPB-I8 AA, AC , and CC genotype frequencies in NRDS group were 11.0％,40.7％, 48.4％ versus 6.6％ , 31.3％ , and 62.1％ in control group, hoth were with no significant difference( P ＞ 0.05 ).The frequencies of A allele were higher in NRDS group than those in control group( 22.3％ v.s 31.3％ ).②The SPB1580 TT, TC , and CC genotype frequencies in NRDS group were 5.5％ , 63.7％ , 45.1％versus 30.8％ , 6.6％ , and 48.4％ in control group, both were with no significant difference( P ＞ 0.05 ).The frequencies of C allele were higher in NRDS group than those in control group ( 79.1％ v.s 70.9％ ).③ The genotype frequencies of 1580 C among Han and American.Brazilian.Dane were 79％ , 35％ , 41％ and 46％( P ＜0.05 ) and 72％ in Japanese( P ＞ 0.05 ).The Genotype frequencies of -18A among Han and American, Brazilian,Dane were 31％ , 58％ ,57％ and 61％( P＜0.05 ).Conclusion The genetic polymorphisms of SPB-I8A/C and SPB1580C/T were the independent risk factors of neonatal respiratory distress syndrome.The polymorphisms of SPB-I8A/C and 1580C/T differ among races.