目的 分析SP-B+1580基因突变与足月新生儿呼吸窘迫综合征(respiratory distress syndrome,RDS)的相关因素。 方法 312例汉族足月RDS新生儿作为RDS组和156例汉族足月健康新生儿作为对照组。PCR扩增 SP-B exon4并测序;免疫组化技术分析肺部SP-B 和proSP-B表达。 结果 两组 SP-B+1580 位点存在CC、C/T、TT 3种基因型,RDS组C/T基因型频率明显高于对照组(P<0.05)。具有C/T基因型的RDS患儿,剖宫产、机械通气、死亡的发生率较其他基因型高,胸片显示RDS程度较重、需要肺表面活性物质的剂量大[200 mg/(kg·次),3~4剂](P<0.01)。50例伴有C/T基因型的RDS死亡患儿中有19例患儿成熟SP-B和proSP-B蛋白肺部表达减少。 结论 SP-B+1580位点C/T基因型可引起成熟SP-B和proSP-B蛋白在肺部的减少,是足月新生儿RDS发病的高危因素。
Abstract
Objective To analyze correlative factor between gene mutation (SP-B +1580) and respiratory distress syndrome(RDS) in full-term newborns. Methods There were 312 Han full-term newborns with RDS as RDS group and 156 Han healthy full-term newborns as control group.Genotypic analysis on exon 4 was performed with polymerase chain reaction amplification(PCR) and gene sequencing.Analysis of for expression of SP-B and proSP-B in lung were determined with immunohistochemical technique. Results Three genotypes of SP-B+1580 including CC,C/T,TT were discovered in two groups.Frequency of C/T genotype in RDS group was higher than that in control group(P<0.05).Patients with C/T genotype had higher rates on uterine-incision delivery mechanical ventilation and mortality chest X-ray grade showed severity about RDS,and needed more pulmonary surfactants(P<0.01).19 patients with decreased mature SP-B and proSP-B were among 50 cases of dead patients with C/T genotypes. Conclusion C/T genotype in SP-B +1580 site causing decreased mature SP-B and proSP-B may be the high risk for RDS.
关键词
呼吸窘迫综合征 /
足月 /
新生儿 /
表面活性物质蛋白B /
基因突变
Key words
respiratory distress syndrome /
full-term /
newborn /
surfactant protein B /
gene mutation
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Floros J,Thomass NJ,Liu W,et al.Family-based association tests suggest linkage between distress syndrome(RDS);SP-B haplotypes and alleles from SP-B-linked loci are risk factors for RDS[J].Pediatr Res,2006,59:616-621.
[2] Sweet DG,Halliday HL.The use of surfactants in 2009[J].Arch Dis Child Educ Pract Ed,2009,94:78-83.
[3] Haataja R,Hallman M.Surfactant proteins as genetic determinants of multifactorial pulmonary diseases[J].Ann Med,2002,34:324-333.
[4] 金汉珍,黄德珉,官希吉.实用新生儿学[M].3版.北京:人民卫生出版社,2003:421-427.
[5] Andreeva AV,Kutuzov MA,Voyno-Yasenetskaya TA.Regulation of surfactant secretion in alveolar type II cells[J].Am J Physiol Lung Cell Mol Physiol,2007,293:L259-L271.
[6] Hawgood S.Surfactant protein B:structure and function[J].Biol Neonate,2004,85:285-289.
[7] Gong MN,Wei Z,Xu LL,et al.Polymorphysm in the surfactant protein-B gene,gender,and the risk of direct pulmonary injury and ARDS[J].Chest,2004,125:203-211. [8] Wilder MA.Surfactant protein B deficiency in infants with respiratory failure[J].J Perinat Neonatal Nurs,2004,18:61-67.
[9] Quasney MW,Waterer GW,Dahmer MK,et al.Association between surfactant protein B +1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia[J].Crit Care Med,2004,32:1115-1119.
[10] Lyral PPR,Diniz EMA,Abe-Sandes K,et al.Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome[J].Braz J Med Biol Res,2011,44(1):66-72.
[11] Lyra1 PPR,Vaz1 FAC,Moreira1 PE,et al.Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome[J].Brazilian J of Med and Biol Res,2007,40:779-786.
[12] Wang G,Christensen ND,Wigdahl B,et al.Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580:implications for disease[J].Biochem J,2003,369:179-184.
[13] Liu W,Bentley CM,Floros J.Study of SP-A,SP-B and SP-D loci:allele frequencys,linkage disquilibrium and heterozygosity in different races and ethnic groups[J].BMC Genet,2003,4:13-20.
基金
国家自然科学基金资助项目(30871397)
PDF(460 KB)
