185 - The Association of Surfactant Proteins A and D Allelic Variants with Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is the primary cause of childhood blindness worldwide. In the US, 15,000 children are annually affected with 500 becoming legally blind. Surfactant proteins A and D (SP-A and SP-D) are lectin proteins that regulate inflammation. We previously showed that SP-A and SP-D are expressed in the retina and that SP-A has a pro-angiogenic phenotype with increased retinal neovascularization. Previous studies showed that allelic single nucleotide polymorphic (SNP) variants in the surfactant proteins genes (SP-A1, SP-A2) are associated with the development 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.  


Objective:

We hypothesize that SP-A1/SP-A2 haplotypes and SP-D SNPs are associated with altered risk of ROP in prematurely born infants. We conducted a pilot study analyzing SP-A1, SP-A2, and SP-D allele variants in a cohort of preterm infants, for association with presence of ROP.


Design/Methods:
Infants born at < 32 weeks’ gestation and/or< 1500 grams were enrolled after birth. Scavenged blood samples or cheek swabs were collected. DNA was extracted from samples using the QIAamp DNA Mini Kit 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 method (previously described). Associations of SP-A1, SP-A2, and SP-D SNP allele frequencies with ROP and BPD were determined using chi-square analysis using the GraphPad Prism Software .


Results:
Of the total patient cohort (n=47), 25 patients had a BPD diagnosis (14 with ROP and 11 without ROP). In the BPD group, patients with the SP-A1 allele 6A⁴ demonstrated significant protection from ROP (OR=0.12, CI= 0.033-0.48, p=0.0021), and patients with the SP-A1 allele 6A2 were at increased risk for ROP (OR=4.75, CI= 1.26-17.4, p=0.0252). The SP-A2 variant 1A2 was also protective for ROP in the BPD group (OR=0.126, CI= 0.01-1.14, p=0.0385).


Conclusion(s):
P-A1/SP-A2 polymorphisms are associated with the presence of ROP in infants with BPD. The 6A⁴ SP-A1 variant and SP-A2 1A2 appear to confer protection in babies against ROP. This protection is independent of BPD status and oxygen exposure and may be related to a direct effect on vascular growth factors. Further studies will determine the mechanism of this protective effect.