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We studied associations of persistent respiratory morbidity (PRM) at 6 and 12 months after acute respiratory failure (ARF) in previously healthy children with single-nucleotide polymorphisms (SNPs) of surfactant protein (SP) genes. Of the 250 enrolled subjects, 155 and 127 were followed at 6 and 12 months after an ARF episode, respectively. Logistic regression analysis and SNP–SNP interaction models were used. We found that 1) in the multivariate analysis, an increased risk at 6 and 12 months was associated with rs1124_A and rs4715_A of  SFTPC , respectively; 2) in a single SNP model, increased and decreased risks of PRM at both timepoints were associated with rs1124 of  SFTPC  and rs721917 of  SFTPD , respectively; an increased risk at 6 months was associated with rs1130866 of  SFTPB  and rs4715 of  SFTPC , and increased and decreased risks at 12 months were associated with rs17886395 of  SFTPA2  and rs2243639 of  SFTPD , respectively; 3) in a two-SNP model, PRM susceptibility at both timepoints was associated with a number of intergenic interactions between SNPs of the studied SP genes. An increased risk at 12 months was associated with one intragenic (rs1965708 and rs113645 of  SFTPA2 ) interaction; 4) in a three-SNP model, decreased and increased risks at 6 and 12 months, respectively, were associated with an interaction among rs1130866 of  SFTPB , rs721917 of  SFTPD , and rs1059046 of  SFTPA2 . A decreased risk at 6 months was associated with an interaction among the same SNPs of  SFTPB  and  SFTPD  and the rs1136450 of  SFTPA1 . The findings revealed that SNPs of all  SFTP s appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children