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Genetic susceptibility for retinopathy of prematurity and its associated comorbidities

Pediatric Research (2024)Cite this article

Abstract

Background

Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants associated with ROP risk and its comorbidities in an Argentinian sample of premature infants.

Methods

A sample of 437 preterm infants <33 weeks GA, born at a maternity hospital in Tucumán, Argentina, 2005–2010, was analyzed. Environmental factors, perinatal outcomes, and fourteen single nucleotide polymorphisms associated with ROP were evaluated, comparing ROP with non-ROP newborns. A lasso logistic regression was performed to select variables; then, a conditional logistic regression was used to identify ROP maternal and perinatal risk factors adjusting by maternal and gestational ages, respectively.

Results

ROP maternal risk factors were alcohol intake, periodontal infections, and severe stress. Respiratory distress, sepsis, and intracranial hemorrhage were the ROP perinatal risk factors. Markers rs186085 of EPAS1 and rs427832 of AGTR1 were significantly associated with ROP newborns.

Conclusion

We identified three maternal and three perinatal risk factors associated with ROP. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP.

Impact

  • Genetic and environmental risk factors associated with ROP and its comorbidities are evaluated in a Latin American population.

  • Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP.

  • Three maternal and three perinatal risk factors associated with ROP were also identified.

  • A matrix of significant relationships among genetic markers and comorbidities is presented.

  • Reported data may help develop more effective preventive measures for ROP in the Latin American region.

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Fig. 1: Text bloks depicts the study inclusion and exclusion criteria.
Fig. 2: Significant relationships among genetic markers and comorbidities of retinopathy of prematurity.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the health care team at Maternidad Nuestra Señora de la Merced, Tucumán, Argentina., for their hard work and support and to Mariana Piola and Alejandra Mariona at ECLAMC who provided technical support.

Funding

The research program was supported by Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-MINCyT), grant numbers PICT-2018-4275 (PI: López Camelo JS) and PICT-2018-4285 (PI: Lucas G. Gimenez), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and INAGEMP [Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)] grant 465549/2014-4.

Author information

Authors and Affiliations

  1. Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC), Centro de Educación Médica e Investigaciones Clínicas-Consejo Nacional de Investigaciones Científicas y Técnicas (CEMIC-CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Lucas G. Gimenez, Juan A. Gili, Darío E. Elias, María R. Santos, Hebe Campaña, Fernando A. Poletta, Julia Ratowiecki, Viviana R. Cosentino, Rocío Uranga, Mónica Rittler & Jorge S. López Camelo

  2. Instituto Nacional de Genética Médica Populacional (INAGEMP), CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina

    Lucas G. Gimenez, Fernando A. Poletta & Jorge S. López Camelo

  3. Instituto Académico Pedagógico de Ciencias Humanas, Universidad Nacional de Villa María, Córdoba, Argentina

    Juan A. Gili

  4. Dirección de Investigación, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina

    Rubén Sagula, Belén Comas, Silvina L. Heisecke, Mercedes Negri & Hugo B. Krupitzki

  5. Instituto Multidisciplinario de Biología Celular, Buenos Aires, Argentina

    María R. Santos

  6. Comisión de Investigaciones Científicas, Buenos Aires, Argentina

    Hebe Campaña

  7. Hospital Interzonal General de Agudos Luisa C. de Gandulfo, Buenos Aires, Argentina

    Viviana R. Cosentino

  8. Hospital San Juan de Dios, Buenos Aires, Argentina

    Rocío Uranga

  9. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes, Tucumán, Argentina

    César Saleme

  10. Hospital Materno Infantil Ramón Sardá, Ciudad Autónoma de Buenos Aires, Argentina

    Mónica Rittler & Jorge Zapata Barrios

  11. Departamento de Neonatología, Clínica y Maternidad Suizo Argentina, Ciudad Autónoma de Buenos Aires, Argentina

    Jorge Zapata Barrios

  12. Instituto Universitario, Centro de Educación Médica e Investigaciones Clínicas (CEMIC-IUC), Ciudad Autónoma de Buenos Aires, Argentina

    Hugo B. Krupitzki

Authors
  1. Lucas G. Gimenez
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  2. Juan A. Gili
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  3. Darío E. Elias
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  4. Rubén Sagula
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  5. Belén Comas
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  17. Hugo B. Krupitzki
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  18. Jorge S. López Camelo
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Contributions

LGG, JAG, and SG made substantial contributions to design, acquisition of data, analysis and interpretation of data, drafting the article and approving the final manuscript as submitted. JSLC, HBK, and JZB made substantial contributions to design, acquisition of data, critical manuscript revision for important intellectual content, and approving of the final version as submitted. DEE, BC, MRS, HC, FAP, SLH, JR, VRC, RU, CS, MN, and MR made contributions to data analysis and interpretation, drafting and editing of the article, and approved the final manuscript as submitted.

Corresponding author

Correspondence to Lucas G. Gimenez.

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Gimenez, L.G., Gili, J.A., Elias, D.E. et al. Genetic susceptibility for retinopathy of prematurity and its associated comorbidities. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03068-9

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