Makri Vassiliki, Hospes Birgit, Stoll-Becker Simone, Borkhardt Arndt, Gortner Ludwig
Department of Paediatrics and Neonatology, University Children's Hospital, Justus-Liebig-University, Feulgenstrasse 12, 35392 Giessen, Germany.
Eur J Pediatr. 2002 Nov;161(11):604-8. doi: 10.1007/s00431-002-1046-1. Epub 2002 Sep 13.
Surfactant protein B (SP-B) is a lipophilic protein and plays a major role in lung mechanics. Polymorphisms of surfactant protein A, another component of the surfactant system, have been previously described to be a risk factor for respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterms. The aim of this prospective study was to determine whether polymorphisms within intron 4 of the SP-B gene are related to the incidence, severity and complications of RDS in Caucasian newborns. In order to identify SP-B intron 4 polymorphisms, we analysed genomic DNA by means of polymerase chain reaction, fragment length and sequence analysis in 140 preterms and 58 healthy term neonates. The frequency of intron 4 variations did not differ between preterms and terms. A total of 111 preterms with the intron 4 wild type (group 1) and 29 preterms carrying the genetic variations (group 2) did not differ in gestational age, gender distribution and birth weight. Compared to group 1, the overall incidence of RDS (75.7% versus 93.1%, P < 0.05), the frequency of severe RDS (28.4% versus 55.2%, P < 0.01) and BPD (21.6% versus 48.3%, P < 0.01) were all higher in group 2. The median duration of oxygen dependency (4 days versus 17 days, P < 0.05) and the need for surfactant administration were also higher in group 2 than in group 1 (43.2% versus 72.4%, P < 0.01). Duration of mechanical ventilation and rate of chronic lung disease at 36 weeks were comparable in both groups.
we suggest that polymorphisms in intron 4 of the surfactant protein B gene independently modify the course of neonatal respiratory distress syndrome.
表面活性蛋白B(SP-B)是一种亲脂性蛋白,在肺力学中起主要作用。表面活性物质系统的另一个成分表面活性蛋白A的多态性,先前已被描述为早产儿呼吸窘迫综合征(RDS)和支气管肺发育不良(BPD)的危险因素。这项前瞻性研究的目的是确定SP-B基因内含子4内的多态性是否与白种人新生儿RDS的发生率、严重程度及并发症相关。为了鉴定SP-B内含子4多态性,我们采用聚合酶链反应、片段长度和序列分析,对140例早产儿和58例健康足月儿的基因组DNA进行了分析。内含子4变异的频率在早产儿和足月儿之间没有差异。111例具有内含子4野生型的早产儿(第1组)和29例携带基因变异的早产儿(第2组)在胎龄、性别分布和出生体重方面没有差异。与第1组相比,第2组RDS的总体发生率(75.7%对93.1%,P<0.05)、重度RDS的频率(28.4%对55.2%,P<0.01)和BPD的频率(21.6%对48.3%,P<0.01)均更高。第2组的中位氧依赖持续时间(4天对17天,P<0.05)和表面活性剂给药需求也高于第1组(43.2%对72.4%,P<0.01)。两组在机械通气持续时间和36周时的慢性肺病发生率方面相当。
我们认为表面活性蛋白B基因内含子4的多态性独立改变新生儿呼吸窘迫综合征的病程。