AUTHOR=Amatya Shaili , Ye Meixia , Yang Lili , Gandhi Chintan K. , Wu Rongling , Nagourney Beth , Floros Joanna 

TITLE=Single Nucleotide Polymorphisms Interactions of the Surfactant Protein Genes Associated With Respiratory Distress Syndrome Susceptibility in Preterm Infants

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.682160

DOI=10.3389/fped.2021.682160

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Neonatal respiratory distress syndrome (RDS), due to surfactant deficiency in preterm infants, is the most common cause of respiratory morbidity. The surfactant proteins (<italic>SFTP</italic>) genetic variants have been well-studied in association with RDS; however, the impact of SNP-SNP (single nucleotide polymorphism) interactions on RDS has not been addressed. Therefore, this study utilizes a newer statistical model to determine the association of <italic>SFTP</italic> single SNP model and SNP-SNP interactions in a two and a three SNP interaction model with RDS susceptibility.</p><p><bold>Methods:</bold> This study used available genotype and clinical data in the Floros biobank at Penn State University. The patients consisted of 848 preterm infants, born &lt;36 weeks of gestation, with 477 infants with RDS and 458 infants without RDS. Seventeen well-studied <italic>SFTPA1, SFTPA2, SFTPB, SFTPC</italic>, and <italic>SFTPD</italic> SNPs were investigated. Wang's statistical model was employed to test and identify significant associations in a case-control study.</p><p><bold>Results:</bold> Only the rs17886395 (C allele) of the <italic>SFTPA2</italic> was associated with protection for RDS in a single-SNP model (Odd's Ratio 0.16, 95% CI 0.06–0.43, adjusted <italic>p</italic> = 0.03). The highest number of interactions (<italic>n</italic> = 27) in the three SNP interactions were among <italic>SFTPA1</italic> and <italic>SFTPA2</italic>. The three SNP models showed intergenic and intragenic interactions among all <italic>SFTP</italic> SNPs except <italic>SFTPC</italic>.</p><p><bold>Conclusion:</bold> The single SNP model and SNP interactions using the two and three SNP interactions models identified <italic>SFTP</italic>-SNP associations with RDS. However, the large number of significant associations containing <italic>SFTPA1</italic> and/or <italic>SFTPA2</italic> SNPs point to the importance of <italic>SFTPA1</italic> and <italic>SFTPA2</italic> in RDS susceptibility.</p>