{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:28Z","timestamp":1785473968032,"version":"3.56.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010751","name":"Fondo Nacional de Desarrollo Cient\u00edfico, Tecnol\u00f3gico y de Innovaci\u00f3n Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007161","name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado, Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"publisher","award":["20260155, 20260152"],"award-info":[{"award-number":["20260155, 20260152"]}],"id":[{"id":"10.13039\/501100007161","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality worldwide. An impaired trophoblast invasiveness and resulting defective remodeling of spiral arteries lead to placental hypoxia that promotes the release of different antiangiogenic and proinflammatory factors to maternal circulation. Adenosine a purine nucleoside derived from ATP metabolism, is among these factors, and high concentrations have been observed in the sera of women affected with PE. The raise in adenosine levels is linked to elevated placental expression of the adenosine A2A receptor (ADORA2A), yet the contribution of single-nucleotide variations (SNVs) in the\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      gene remains unclear. The association between placental\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      SNVs and preeclampsia was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Five SNVs (rs2298383, rs4822489, rs2236624, rs17650937, and s8192446) were genotyped using real-time PCR with TaqMan probes. The functional effect of the N144K mutation was evaluated through\n                      <jats:italic>in silico<\/jats:italic>\n                      mutagenesis to assess potential structural alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The SNV rs8192446 was strongly associated with PE [OR=10.42 (95% CI: 2.08\u2013103.39, p=0.0009)], association that remained after BH correction (p=0.0009). The SNV rs8192446 was also associated with mild PE (p=0.0403) and severe PE (p=0.0072).\n                      <jats:italic>In-silico<\/jats:italic>\n                      results revealed that N144K mutation does not alter the recognition of the ligand by\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      but exerts a subtle modulation of the\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      \u2013adenosine interaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Taken together, these results suggest that placental\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      rs8192446 is functionally relevant for preeclampsia development contributing to\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      hypofunction through perturbations in downstream signaling mechanisms. This is the first study to report an association between\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      rs8192446 and preeclampsia susceptibility in Mexican population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1843298","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:25:32Z","timestamp":1785471932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental SNV rs8192446 in the ADORA2A gene is associated with Preeclampsia: a pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Perla","family":"Valenzuela-Torres","sequence":"first","affiliation":[{"name":"National Polytechnic Institute (IPN), CIIDIR-Durango, Academia de Gen\u00f3mica","place":["Durango, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Sosa-Mac\u00edas","sequence":"additional","affiliation":[{"name":"National Polytechnic Institute (IPN), CIIDIR-Durango, Academia de Gen\u00f3mica","place":["Durango, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Felipe","family":"Burgos","sequence":"additional","affiliation":[{"name":"Universidad de Concepcion Departamento de Fisiologia","place":["Concepci\u00f3n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia E.","family":"Damiano","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas, facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires","place":["Buenos Aires, Argentina"]},{"name":"IFIBIO Houssay-CONICET Universidad de Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Reynoso","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas, facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires","place":["Buenos Aires, Argentina"]},{"name":"IFIBIO Houssay-CONICET Universidad de Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Simental-Mend\u00eda","sequence":"additional","affiliation":[{"name":"Instituto Mexicano del Seguro Social, Unidad de Investigaci\u00f3n Durango","place":["Durango, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesenia","family":"Acurio","sequence":"additional","affiliation":[{"name":"Vascular Physiology Laboratory, Department of Basic Science, Universidad del Bio Bio","place":["Chill\u00e1n, Chile"]},{"name":"Consortium for Research and Innovation Neurovascular, (NEUROVAS)","place":["Chill\u00e1n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence A.","family":"Marchat","sequence":"additional","affiliation":[{"name":"Instituto Politecnico Nacional Escuela Nacional de Medicina y Homeopatia","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alonso","family":"Escudero","sequence":"additional","affiliation":[{"name":"Vascular Physiology Laboratory, Department of Basic Science, Universidad del Bio Bio","place":["Chill\u00e1n, Chile"]},{"name":"Consortium for Research and Innovation Neurovascular, (NEUROVAS)","place":["Chill\u00e1n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Galaviz-Hernandez","sequence":"additional","affiliation":[{"name":"National Polytechnic Institute (IPN), CIIDIR-Durango, Academia de Gen\u00f3mica","place":["Durango, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11302-016-9538-z","article-title":"Adenosine A2A receptor regulates expression of vascular endothelial growth factor in feto-placental endothelium from normal and late-onset pre-eclamptic pregnancies","volume":"13","author":"Acurio","year":"2017","journal-title":"Purinergic Signalling"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1097\/01.AOG.0000437382.03963.88","article-title":"Hypertension in pregnancy","volume":"122","year":"2013","journal-title":"Obstetrics Gynecology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.795309","article-title":"Evaluation of the PLAC8 gene in Mexican women with and without preeclampsia and obesity","volume":"9","author":"Barrag\u00e1n-Z\u00fa\u00f1iga","year":"2022","journal-title":"Front. 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