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Surfactant proteins A and D (SP-A and SP-D) play an immunomodulatory role. We previously reported the impact of SP-A on retinal angiogenesis. This study investigates SP-A and SP-D single-nucleotide polymorphisms (SNPs) with risk of ROP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Subjects were infants with gestational age (GA) of &lt;32 weeks and\/or birth weight &lt;1500 grams. DNA from blood was used to genotype the SNPs. Statistical analysis used logistic regression for the association of ROP with genetic and clinical factors, including bronchopulmonary dysplasia (BPD), GA, and oxygen exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 59 infants were enrolled. In the whole cohort, the SFTPA1 SNP rs1059057 \u2018G\u2019 allele was associated with increasing odds of ROP when controlling for GA and oxygen. In both the whole cohort and in BPD, the SFTPA2 SNP rs1965707 \u2018T\u2019 allele was associated with increasing odds of ROP risk when controlling for GA and oxygen. Furthermore, there was an interaction effect where the protective effect of GA in the presence of the wildtype (C\/C) was diminished in the presence of the \u2018T\u2019 allele.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study identifies novel associations between surfactant protein gene SNPs and ROP risk that may impact protein structure, function in the retinal vasculature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Retinopathy of Prematurity (ROP) stems from disrupted angiogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Surfactant protein A (SP-A) impacts retinal vascular disease, but associations between genetic polymorphisms of surfactant proteins (SPs) and ROP are unknown.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We report novel surfactant protein polymorphisms and ROP. The risk of ROP modeled by controlling for gestational age (GA) and oxygen suggests novel direct effects on endothelial function and angiogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The resultant amino acid substitutions were mapped to predict translational protein modifications.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>As SNPs alter amino acid structure, protein folding, and functionality, our results provide critical mechanistic clues for vascular diseases of prematurity. Mapping of genetic signatures enables earlier detection of ROP.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04435-w","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:48Z","timestamp":1760632428000},"page":"2055-2065","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surfactant proteins A and D nucleotide variants: association with retinal vascular disease"],"prefix":"10.1038","volume":"99","author":[{"given":"Kelsey Brass","family":"Allen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin","family":"Rousselle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Aston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishla Col\u00f3n","family":"Monta\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Silveyra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Michael","family":"Siatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Vitiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-5291","authenticated-orcid":false,"given":"Faizah N.","family":"Bhatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"4435_CR1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1001\/jamaophthalmol.2023.0809","volume":"141","author":"A Bhatnagar","year":"2023","unstructured":"Bhatnagar, A., Skrehot, H. 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