{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:05:15Z","timestamp":1788998715114,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012874","name":"College of Medicine, University of Central Florida","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012874","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2022,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Environmental factors may influence the development of tetralogy of Fallot (TOF), and DNA methylation patterns may reveal specific chemical signatures of perturbations during cardiac development. We investigated whether blood and buccal cells could be viable surrogates for myocardium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured epigenome\u2010wide DNA methylation at 866,895 5\u2019\u2010cytosine\u2010phosphate\u2010guanine\u20103\u2019 (CpG) sites in blood (n=3), buccal cells (n=3), and right ventricular myocardium (n=4) collected from infants with TOF and compared the percent of differentially methylated CpG sites across tissue types. Gene\u2010specific DNA methylation profiles were also analyzed for ten representative genes associated with heart development. Welch's ANOVAs compared general methylation between tissue types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparison of DNA methylation profiles across blood, buccal, and myocardium suggested myocardium and buccal samples were most similar, differing in DNA methylation at only 1.3% (11,386) of CpG sites whereas myocardium and blood were most dissimilar, having 146,857 statistically dissimilar methylated CpG sites (~17% dissimilarity; adjusted <jats:italic>p<\/jats:italic> &lt; 0.01 for each site). Buccal swabs were significantly more variable (<jats:italic>p<\/jats:italic> &lt; .001) than either blood or myocardial samples. In gene\u2010specific analyses, <jats:italic>SCO2<\/jats:italic>, <jats:italic>GATA4<\/jats:italic>, <jats:italic>NOTCH4<\/jats:italic>, <jats:italic>WNT7A<\/jats:italic>, and <jats:italic>DKK2<\/jats:italic> showed conserved DNA methylation profiles across tissue types, while <jats:italic>HAND1<\/jats:italic>, <jats:italic>JAG1<\/jats:italic>, <jats:italic>NKX2\u20105<\/jats:italic>, <jats:italic>TBX5<\/jats:italic> and <jats:italic>TBX20<\/jats:italic> showed more distinctive tissue\u2010specific patterns of DNA methylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Compared with blood, buccal tissue more closely mirrors the myocardial methylome, with &gt;10\u2010fold similarity. Nevertheless, both buccal and blood tissue capture highly conserved DNA methylation patterns at specific genetic loci related to cardiac development.<\/jats:p><jats:p>Buccal cheek swabs may be a useful surrogate tissue type for future investigations of TOF\u2010specific epigenetic profiles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2090","type":"journal-article","created":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T09:29:31Z","timestamp":1663406971000},"page":"1101-1111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparison of <scp>DNA<\/scp> methylation patterns across tissue types in infants with tetralogy of Fallot"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-1125","authenticated-orcid":false,"given":"Jennifer S.","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Services Nemours Children's Health  Orlando Florida USA"},{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheuk","family":"Kwok","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Braganca","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daralys L.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea P.","family":"Espina Rey","sequence":"additional","affiliation":[{"name":"Department of Faculty &amp; Academic Affairs, University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven N.","family":"Ebert","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Sciences, Burnett School of Biomedical Sciences University of Central Florida College of Medicine  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14880"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60657-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21231"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.06.025"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120213-092518"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-020-00848-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000602"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.2.163"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34187"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-016-0697-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01827"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4601.098427"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-019-0534-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw195"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04989-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(02)01886-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2003.05.003"},{"issue":"1","key":"e_1_2_9_19_1","first-page":"29","article-title":"Focus on: Epigenetics and fetal alcohol spectrum disorders","volume":"34","author":"Kobor M. 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