Floros J, Veletza S V, Kotikalapudi P, Krizkova L, Karinch A M, Friedman C, Buchter S, Marks K
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033.
Biochem J. 1995 Jan 15;305 ( Pt 2)(Pt 2):583-90. doi: 10.1042/bj3050583.
Pulmonary surfactant, a lipoprotein complex, is essential for normal lung function, and deficiency of surfactant can result in respiratory-distress syndrome (RDS) in the prematurely born infant. Some studies have pointed towards a genetic contribution to the aetiology of RDS. Because the surfactant protein B (SP-B) is important for optimal surfactant function and because it is involved in the pathogenesis of pulmonary disease, we investigated the genetic variability of the SP-B gene in individuals with and without RDS. We identified a 2.5 kb BamHI polymorphism and studied its location, nature and frequency. We localized this polymorphism in the first half of intron 4 and found that it is derived by gain or loss in the number of copies of a motif that consists of two elements, a 20 bp conserved sequence and a variable number of CA dinucleotides. Variability in the number of motifs resulting from either deletion (in 55.3% of the cases with the variation) or insertion (44.7%) of motifs was observed in genomic DNAs from unrelated individuals. Analysis of 219 genomic DNAs from infants with (n = 82) and without (n = 137) RDS showed that this insertion/deletion appears with significantly higher frequency in the RDS population (29.3 as against 16.8%, P < 0.05).
肺表面活性物质是一种脂蛋白复合物，对正常肺功能至关重要，表面活性物质缺乏可导致早产婴儿发生呼吸窘迫综合征（RDS）。一些研究指出遗传因素在RDS病因学中起作用。由于表面活性蛋白B（SP-B）对最佳表面活性物质功能很重要，且参与肺部疾病的发病机制，我们研究了患RDS和未患RDS个体中SP-B基因的遗传变异性。我们鉴定出一个2.5kb的BamHI多态性，并研究了其位置、性质和频率。我们将此多态性定位在内含子4的前半部分，发现它是由一个由两个元件组成的基序拷贝数的增减导致的，这两个元件分别是一个20bp的保守序列和可变数量的CA二核苷酸。在无关个体的基因组DNA中观察到，由于基序的缺失（55.3%的变异病例）或插入（44.7%）导致基序数量的变异性。对219例患RDS（n = 82）和未患RDS（n = 137）婴儿的基因组DNA分析显示，这种插入/缺失在RDS人群中的出现频率显著更高（分别为29.3%和16.8%，P < 0.05）。
