新生儿呼吸窘迫综合征SP-B＋1580基因表达及遗传多态性分析  

Expression and polymorphism of surfactant protein B gene +1580 in neonatal respiratory distress syndrome

作　　者：曲雯雯[1,2] 范含笑[1] 谢露[1] 王钰[1] 魏巍[1] 尹晓娟[1,2] 

机构地区：[1]北京军区总医院附属八一儿童医院新生儿科,北京100700 [2]北京军区总医院大连医科大学临床学院,北京100700

出　　处：《第三军医大学学报》2012年第20期2070-2074,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金(30871397)~~

摘　　要：目的探讨新生儿呼吸窘迫综合征肺表面活性物质蛋白B的基因突变类型及基因型频率。方法在北京地区选择无血缘关系的汉族新生儿RDS 40例作为RDS组,汉族40例其他病例作为对照组,以胎龄与RDS组相匹配。免疫组化检测SP-B蛋白在肺部细胞的表达,Western blot检测SP-B蛋白在肺部和支气管肺泡灌洗液的表达,PCR及基因测序技术分析SP-B+1 580位点的基因突变。结果 RDS组SP-B蛋白表达阳性细胞数显著低于对照组(t=10.191,P<0.01)。RDS组中,8例肺组织和支气管肺泡灌洗液成熟SP-B蛋白表达同时减少,7例仅支气管肺泡灌洗液成熟SP-B蛋白表达减少。2组SP-B基因+1 580位点均存在纯合和杂合基因突变,RDS组占20例,12例为纯合突变(C/C),8例为杂合突变(C/T);对照组占8例,1例为纯合突变(C/C),7例为杂合突变C/T。RDS组C/C基因型频率为30.0%,C/T基因型频率为20.0%;对照组C/C基因型频率为2.5%,C/T基因型频率为1.75%。RDS组C/C基因型频率较对照组显著增高(χ2=11.114,P<0.01)。结论新生儿呼吸窘迫综合征SP-B+1 580位点存在纯合和杂合基因突变两种类型,其纯合突变(C/C)可能参与了RDS的发病。Objective To investigate the types of mutation and genotypic frequency of surfactant protein B（SP-B） in neonatal respiratory distress syndrome（RDS）.Methods Unrelated 40 cases with neonatal RDS of Han ethnic group in Beijing region in our department from August 2006 to April 2011 were selected as RDS group,while unrelated 40 other cases of Han ethnic group in same period were selected as control group.Two groups matched with gestational age.Expression of SP-B in lung cells was tested with immunohistochemical assay.Expression of SP-B in lung tissue and bronchoalveolar lavage fluid（BALF） was determined with Western blotting.Types of genetic mutations in SP-B ＋ 1 580 locus were screened with polymerase chain reaction（PCR） and gene sequencing.Results The number of SP-B positive cells were less in RDS group than in control group（t = 10.191,P〈0.01）.Eight cases in RDS group simultaneously had lower expression level of mature SP-B in lung tissue and BALF,while 7 cases in the same group had lower level of mature SP-B only in BALF.Genetic mutations including homozygous and heterozygous mutation existed in SP-B exon 4 of both 2 groups,which located in ＋ 1 580 site of SP-B gene.Twenty cases had gene mutation of SP-B in RDS group,including 12 homozygous mutations with C/C genotypes and 8 heterozygous mutations with C/T genetic types.Eight cases had gene mutations of SP-B ＋ 1 580 in control group including 1 homozygous mutation with C/C genotype and 7 heterozygous mutations with C/T genotypes.Genotypic frequency of homozygous mutation（C/C） of SP-B ＋1 580 in RDS group was 30.0% while that of heterozygous mutation（C/T） was 20.0%.Genotypic frequency of homozygous mutation（C/C） of SP-B ＋ 1 580 in control group was 2.5% while that of heterozygous mutation（C/T） was 1.75%.Genotypic frequency of heterozygous mutation（C/C） in RDS group had higher level than that in control group（Chi square = 11.114,P〈0.01）.Conclusion Genetic mutations including homozygous and heterozygous mutatio

关 键 词：新生儿 呼吸窘迫综合征 肺表面活性物质蛋白B 基因突变 

分 类 号：R394.2[医药卫生—医学遗传学] R722.12[医药卫生—基础医学]