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

Abstract

<b>Background:</b> Neonatal respiratory distress syndrome (RDS), due to surfactant deficiency in preterm infants, is the most common cause of respiratory morbidity. The surfactant proteins (<i>SFTP</i>) 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 <i>SFTP</i> single SNP model and SNP-SNP interactions in a two and a three SNP interaction model with RDS susceptibility. <b>Methods:</b> This study used available genotype and clinical data in the Floros biobank at Penn State University. The patients consisted of 848 preterm infants, born <36 weeks of gestation, with 477 infants with RDS and 458 infants without RDS. Seventeen well-studied <i>SFTPA1, SFTPA2, SFTPB, SFTPC</i>, and <i>SFTPD</i> SNPs were investigated. Wang's statistical model was employed to test and identify significant associations in a case-control study. <b>Results:</b> Only the rs17886395 (C allele) of the <i>SFTPA2</i> was associated with protection for RDS in a single-SNP model (Odd's Ratio 0.16, 95% CI 0.06-0.43, adjusted <i>p</i> = 0.03). The highest number of interactions (<i>n</i> = 27) in the three SNP interactions were among <i>SFTPA1</i> and <i>SFTPA2</i>. The three SNP models showed intergenic and intragenic interactions among all <i>SFTP</i> SNPs except <i>SFTPC</i>. <b>Conclusion:</b> The single SNP model and SNP interactions using the two and three SNP interactions models identified <i>SFTP</i>-SNP associations with RDS. However, the large number of significant associations containing <i>SFTPA1</i> and/or <i>SFTPA2</i> SNPs point to the importance of <i>SFTPA1</i> and <i>SFTPA2</i> in RDS susceptibility.