{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:55:46Z","timestamp":1760057746403,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF21OC0067235","LONG-COVID-EXP-CM"],"award-info":[{"award-number":["NNF21OC0067235","LONG-COVID-EXP-CM"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo Europeo De Desarrollo Regional","award":["NNF21OC0067235","LONG-COVID-EXP-CM"],"award-info":[{"award-number":["NNF21OC0067235","LONG-COVID-EXP-CM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genetics and epigenetics are mechanisms proposed for explaining post-COVID-19 condition. This secondary analysis aimed to investigate if DNA methylation levels of the ACE2 promoter are different depending on the genotype of five COVID-19-related polymorphisms in individuals who had been previously hospitalized due to SARS-CoV-2 infection. We collected non-stimulated saliva samples from 279 (48.7% female, age: 56.0 \u00b1 12.5 years) previously hospitalized COVID-19 survivors. The participants self-reported for the presence of post-COVID symptomatology that started after the infection and persisted at the time of the appointment. Three potential genotypes of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, and ACE1 rs1799752 polymorphisms were identified from saliva samples. Further, methylation levels at five different locations (CpG) of dinucleotides in the ACE2 promoter were quantified using bisulfited pyrosequencing. Differences in the methylation percentage (%) of each CpG according to the genotype of the five polymorphisms were analyzed. Participants were evaluated up to 17.8 (SD: 5.2) months after hospital discharge. Eighty-eight percent (88.1%) of patients reported at least one post-COVID symptom (mean number of post-COVID symptoms: 3.0; SD: 1.9). Overall, we did not observe significant differences in the methylation levels of the ACE2 promoter according to the genotype of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, or ACE1 rs1799752 single nucleoid polymorphisms. This study did not find an association between genetics (genotypes of five COVID-19-associated polymorphisms) and epigenetics (methylation levels of the ACE2 promoter) in a cohort of COVID-19 survivors with post-COVID-19 condition who were hospitalized during the first wave of the pandemic.<\/jats:p>","DOI":"10.3390\/ijms26052100","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:13:58Z","timestamp":1740633238000},"page":"2100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA Salivary Methylation Levels of the ACE2 Promoter Are Not Related to ACE2 (rs2285666 and rs2074192), TMPRSS2 (rs12329760 and rs2070788) and ACE1 rs1799752 Polymorphisms in COVID-19 Survivors with Post-COVID-19 Condition"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9690","authenticated-orcid":false,"given":"C\u00e9sar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"},{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-1490","authenticated-orcid":false,"given":"Gema","family":"D\u00edaz-Gil","sequence":"additional","affiliation":[{"name":"Research Group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28933 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-5831","authenticated-orcid":false,"given":"Antonio","family":"Gil-Crujera","sequence":"additional","affiliation":[{"name":"Research Group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28933 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-4286","authenticated-orcid":false,"given":"Stella M.","family":"G\u00f3mez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Research Group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28933 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6755-8189","authenticated-orcid":false,"given":"Silvia","family":"Ambite-Quesada","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-6837","authenticated-orcid":false,"given":"Juan","family":"Torres-Macho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain"},{"name":"Department of Medicine, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4212-7419","authenticated-orcid":false,"given":"Pablo","family":"Ryan-Murua","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), ISCIIII, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-0200","authenticated-orcid":false,"given":"Ana I.","family":"Franco-Moreno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de la Torre, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-1029","authenticated-orcid":false,"given":"Oscar J.","family":"Pellicer-Valero","sequence":"additional","affiliation":[{"name":"Image Processing Laboratory (IPL), Universitat de Val\u00e8ncia, Parc Cient\u00edfic, 46100 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1579","authenticated-orcid":false,"given":"Lars","family":"Arendt-Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"},{"name":"Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-129X","authenticated-orcid":false,"given":"Rocco","family":"Giordano","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, February 15). 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