OBJECTIVE:To study the relationship between SP-A2 and SP-B gene polymorphisms and respiratory distress syndrome in preterm neonates. DESIGN:Cross-sectional. SETTING:Neonatal intensive care unit and the unit of the Chemical Pathology Department, Kasr Alainy hospital, Cairo University. PARTICIPANTS:Sixty-five preterm infants with respiratory distress syndrome and 50 controls. The genomic DNA was isolated using DNA extraction kits. SYBR Green-based real-time PCR was used to determine the variant genotypes of SP-A2 c.751 G>A and SP-B c.8714 G>C single nucleotide polymorphisms. RESULTS:Homozygosity of SP-A (OR 46, 95% CI 14-151) and SP-B (OR 5.2, 95% CI 2.3-11.4) alleles increased the risk of respiratory distress syndrome. The logistic regression model showed that genotypes SP-A2 (OR 164) and SP-B (OR 18) were directly related to the occurrence of respiratory distress syndrome, whereas gestational age (OR 0.57) and 5-minute Apgar score (OR 0.19) were inversely related to its occurrence. CONCLUSIONS:There is a possible involvement of SP-A2 and SP-B genes polymorphisms in the genetic predisposition to respiratory distress syndrome.