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Abstract Background: Respiratory distress syndrome (RDS) of the newborn is the most common cause of morbidity and mortality. Its pathophysiology is complex, In addition to environmental factors; genetic factors may participate in RDS risk. Aims: To assess potential association of SP-C gene rs1124 polymorphism with RDS development and severity in a group of Egyptian preterm newborns. Methods: One hundred preterm neonates were enrolled in a prospective case control study. 50 neonate s were with RDS and 50 neonates as a control group. Detailed history and clinical examination data were recorded. Respiratory distress (RD) was scored according to Downes{u2019} scoring system. Genotyping was performed by PCR-RFLP method. Results: There were no statistical significant difference in GG, AG &AA genotypes or A & G alleles frequencies of SFTPC rs1124 among RDS neonates and controls. Also there were no statistical significant differences of genotyping frequencies and severity of RDS. Decreased gestational age was the most important factors in predisposition to RDS. Conclusion: No association of SP-C gene rs1124 polymorphism with RDS development and severity of the disease in Egyptian preterm newborns |