Diagnostics (Aug 2023)

Association of the <i>EPAS1</i> rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen

  • Diana G. Rogel-Ayala,
  • José Esteban Muñoz-Medina,
  • Valeria Dejanira Vicente-Juárez,
  • Patricia Grether-González,
  • Deneb Algedi Morales-Barquet,
  • Alfonso de Jesús Martínez-García,
  • María Olga Leticia Echaniz-Aviles,
  • Rosalba Sevilla-Montoya,
  • Alejandro Martínez-Juárez,
  • Jazmin Artega-Vázquez,
  • Javier Angeles-Martínez,
  • Gilberto Vargas-Alarcón,
  • Alberto Hidalgo-Bravo,
  • Irma Eloisa Monroy-Muñoz

DOI
https://doi.org/10.3390/diagnostics13152558
Journal volume & issue
Vol. 13, no. 15
p. 2558

Abstract

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Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

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