164 - The Association Of Surfactant Protein A And D Allelic Variants With Retinopathy Of Prematurity: Update And Completion Of Preliminary Analysis

Poster Number: 164
Publication Number: 164.2819

Background: Retinopathy of prematurity (ROP) is the primary cause of childhood blindness with 15,000 children affected annually in the US with 500 becoming legally blind. Surfactant proteins A and D (SP-A and SP-D) inflammation. Previous studies showed that allelic single nucleotide polymorphic (SNP) variants in the surfactant proteins genes (SP-A1, SP-A2 and SP-D) are associated with severity of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). The SP-A1/SP-A2 haplotype 6A2/1A0 and the SP-D/SP-A2 locus DA160 A/SP-A2 1A1 confer protection from severe disease. Our preliminary data showed that 6A4 SP-A1 variant and SP-A2 1A2 protected babies against ROP when controlling for BPD.

Objective: We hypothesize that. SP-A1/SP-A2 haplotypes and SP-D SNPs alter the risk of ROP in preterm infants. Our pilot study analyzed SP-A1, SP-A2, and SP-D allele variants in a cohort of preterm infants for association with ROP. We now have completion of data with addition of more subjects to our original cohort to validate our results.

Design/Methods: Infants born at < 32 weeks’ GA and/or < 1500 grams were enrolled after birth. Scavenged blood samples or cheek swabs were collected for DNA extracted and stored at -80C. Clinical data included BPD status, presence of ROP, and total days on supplemental oxygen. SNPs were measured with Taqman probes for allelic discrimination by PCR or PCR/RFLP/sequencing. Associations of SP-A1, SP-A2, and SP-D SNP allele frequencies with ROP were determined using chi-square and logistic regression analysis controlling for BPD.

Results: Of the total patient cohort (n=59), 39% of babies had any stage of ROP, 42 patients had BPD (21 with ROP and 21 without ROP). There was no association of sex, race. BPD, gestational age and Days O2 were significantly associated with ROP (p < 0.0.013 OR 7.5 CI 1.01-1.0-5). Analyzing only the BPD group, patients with the none of the SP-A1 alleles conferred risk or protection. The SP-A2 allele 1A2 conferred protection against ROP in the co-dominant model (p=0.0055) with risk decreases with each additional 1A2, with when controlling for days on oxygen. For SP-D, both aa11 and aa160 increased risk of ROP in both models (p < 0.005).

Conclusion(s): SP-A2 and SP-D polymorphisms confirm protection for infants against ROP. The 6A4 SP-A1 did not protect as it did in our preliminary analysis or as it reported in the literature, however SP-A2 1A2 conferred protection against ROP independent of BPD or oxygen exposure and may be related to a direct effect on vascular growth factors. We are now evaluating protein levels and mechanistic roles of 1A2 polymorphism.