Surfactant protein C gene variation in the Finnish population - association with perinatal respiratory disease
Surfactant protein C gene variation in the Finnish population - association with perinatal respiratory disease
复制标题
DOI：
10.1038/sj.ejhg.5201137
复制
发表时间：
2004-04-01
影响因子：
5.2
通讯作者：
Hallman, M
中科院分区：
文献类型：
--
作者：
Lahti, M;Marttila, R;Hallman, M
表面活性蛋白C（SP-C）是肺泡表面活性物质的一种小分子疏水蛋白组分，是肺肺泡表面的一种脂质蛋白复合物。表面活性物质缺乏是早产儿呼吸窘迫综合征（RDS）的主要原因。RDS是一种称为支气管肺发育不良（BPD）的慢性肺病的主要危险因素。SP-C基因的显性突变最近被认为与间质性肺疾病有关。然而，表面活性蛋白C基因中常见的遗传变异尚未得到详细研究。在本研究中，定义了芬兰人群（n = 472）中SP-C基因的外显子变异，并研究了等位基因变异与RDS和BPD易感性的关系。构象敏感凝胶电泳（CSGE）用于确定SP-C基因外显子变异的程度。对编码proSP-C的SP-C基因外显子1、4和5的三个双等位基因多态性产生基因分型方法。这些多态性的频率进行了评估，在一个研究人口组成的158个DNA样本，从足月婴儿。此外，通过父母-婴儿三联体的单倍型分析来评估SP-C等位基因之间的连锁不平衡。SP-C基因变异在RDS和BPD中的作用在245名早产儿的高危人群中进行了评估。根据目前的结果，SP-C基因多态性与RDS和极早产有关。等位基因关联的强度根据早产儿的性别而不同。
Surfactant protein C (SP-C) is a small hydrophobic protein component of alveolar surfactant, a lipid protein complex lining the alveolar surface of the lung. Surfactant deficiency is the main cause of respiratory distress syndrome (RDS) in premature infants. RDS is a major risk factor of a chronic lung disease called bronchopulmonary dysplasia (BPD). The dominant mutations of the SP-C gene have recently been associated with interstitial lung diseases. However, the common genetic variation in the surfactant protein C gene has not been studied in detail. In the present study, the exonic variation of the SP-C gene in the Finnish population (n = 472) was defined, and the association of the allelic variants with the susceptibility to RDS and BPD was examined. Conformation-sensitive gel electrophoresis (CSGE) was used to determine the extent of exonic variation in the SP-C gene. Methods of genotyping were generated for three biallelic polymorphisms of the SP-C gene's exons 1, 4 and 5, which encode proSP-C. The frequencies of these polymorphisms were evaluated in a study population consisting of 158 DNA samples from fullterm infants. In addition, the linkage disequilibrium between the SP-C alleles was evaluated by haplotype analysis of parent - infant triplets. The role of SP-C gene variation in RDS and in BPD was evaluated in a high-risk population of 245 premature infants. According to the present results, the SP-C polymorphisms were associated with RDS and with very premature birth. The strength of allelic associations differed according to the gender of the premature infants.