Retinopathy of prematurity (ROP) is the primary cause of childhood blindness worldwide. Previous studies showed that allelic single nucleotide polymorphic (SNP) variants of the human surfactant protein A genes (SP-A1, SP-A2) are associated with the development of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). In this work, we hypothesized that SP-A SNPs and allelic variants are associated with altered risk of ROP in prematurely born infants. To test this hypothesis, we used a modified PCR-based method to detect variants of the SP-A1 and SP-A2 genes in a cohort of preterm infants. Infants born at <32 weeks’ gestation and/or<1500 grams were enrolled. Scavenged blood samples or cheek swabs were collected and DNA was extracted using the QIAamp DNA Mini Kit. We measured SNPs in SP-A1 and SP-A2 using Taqman probes for allelic discrimination by PCR or PCR/RFLP/sequencing method. Associations of SP-A1 and SP-A2 SNP allele frequencies with ROP and BPD were determined using chi-square and logistic regression analyses. Our results show that, of the total patient cohort (n=59), 42 patients had a BPD diagnosis (23 with ROP and 36 without ROP). DNA analysis of these samples identified associations of SP-A1 and SP-A2 SNPs and variants with ROP. For SP-A1, the following SNP associations were found for ROP using chi-square: rs1059047 (p=0.44), rs1136450 (p=0.63), rs1136451 (p=0.21), rs1059057 (p=0.52). For SP-A2, the following SNPs associations were identified with ROP: rs1059046 (p=0.51), rs17886395 (p=0.050), rs1965707 (p=0.031), rs1965708 (p=0.46). Logistic regression analysis indicated an association of ROP with the SP-A1 6A2 variant (p-value = 0.47, OR (6A2/*)=0.8036, 95%CI [0.2299 - 2.8082], OR (6A2/6A2) = 0.4327, 95%CI [0.1063 - 1.7615]), which conferred protection, as well as an association of ROP with SP-A2 6A2 (p-value = 0.0055) with decreased risk when 1A2 variant is present. We conclude that SP-A1/SP-A2 polymorphisms are associated with the presence of ROP in infants with BPD. The 6A4 SP-A1 and SP-A2 1A2 appear to confer protection in babies against ROP. Further studies will determine the mechanisms of this protective effect. Indiana University, University of Chicago Metcalf Internship Program Grant, The University of Oklahoma Health Sciences Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.