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

Neonatal respiratory distress syndrome (RDS), due to surfactant deficiency in preterm infants, is the most common cause of respiratory morbidity. The surfactant proteins () 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 single SNP model and SNP-SNP interactions in a two and a three SNP interaction model with RDS susceptibility. 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 , and SNPs were investigated. Wang's statistical model was employed to test and identify significant associations in a case-control study. Only the rs17886395 (C allele) of the was associated with protection for RDS in a single-SNP model (Odd's Ratio 0.16, 95% CI 0.06-0.43, adjusted = 0.03). The highest number of interactions ( = 27) in the three SNP interactions were among and . The three SNP models showed intergenic and intragenic interactions among all SNPs except . The single SNP model and SNP interactions using the two and three SNP interactions models identified -SNP associations with RDS. However, the large number of significant associations containing and/or SNPs point to the importance of and in RDS susceptibility.