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

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

doi:10.3389/fgene.2022.815727

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

Front Genet. 2022 Mar 24:13:815727. doi: 10.3389/fgene.2022.815727. eCollection 2022.

Authors

Chintan K Gandhi¹, Neal J Thomas¹, Ye Meixia², Debbie Spear¹, Chenqi Fu³, Shouhao Zhou³, Rongling Wu³, Garrett Keim⁴, Nadir Yehya⁴, Joanna Floros^{1

5}

Affiliations

¹ Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, United States.
² Center for Computational Biology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
³ Public Health Science, Pennsylvania State University College of Medicine, Hershey, PA, United States.
⁴ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
⁵ Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, PA, United States.

Abstract

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 SFTPs appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.

Keywords: SNP–SNP interaction; long-term outcomes of pediatric acute respiratory failure; pediatric acute respiratory failure; persistent respiratory morbidity; surfactant protein genetic variant.