AUTHOR=Gandhi Chintan K. , Thomas Neal J. , Meixia Ye , Spear Debbie , Fu Chenqi , Zhou Shouhao , Wu Rongling , Keim Garrett , Yehya Nadir , Floros Joanna 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.815727

DOI=10.3389/fgene.2022.815727

ISSN=1664-8021

ABSTRACT=<p>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 <italic>SFTPC</italic>, respectively; 2) in a single SNP model, increased and decreased risks of PRM at both timepoints were associated with rs1124 of <italic>SFTPC</italic> and rs721917 of <italic>SFTPD</italic>, respectively; an increased risk at 6 months was associated with rs1130866 of <italic>SFTPB</italic> and rs4715 of <italic>SFTPC</italic>, and increased and decreased risks at 12 months were associated with rs17886395 of <italic>SFTPA2</italic> and rs2243639 of <italic>SFTPD</italic>, 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 <italic>SFTPA2</italic>) 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 <italic>SFTPB</italic>, rs721917 of <italic>SFTPD</italic>, and rs1059046 of <italic>SFTPA2</italic>. A decreased risk at 6 months was associated with an interaction among the same SNPs of <italic>SFTPB</italic> and <italic>SFTPD</italic> and the rs1136450 of <italic>SFTPA1</italic>. The findings revealed that SNPs of all <italic>SFTP</italic>s appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.</p>