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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 full-term 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.

Surfactant protein C gene variation in the Finnish population – association with perinatal respiratory disease