{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:59:18Z","timestamp":1789603158967,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2009-1606229"],"award-info":[{"award-number":["GR-2009-1606229"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions. MTHFR hypermethylation, resulting in reduced gene expression, can contribute to several human disorders, but little is still known about the factors that regulate MTHFR methylation levels. We performed the present study to investigate if common polymorphisms in one-carbon metabolism genes contribute to MTHFR methylation levels. MTHFR methylation was assessed in peripheral blood DNA samples from 206 healthy subjects with methylation-sensitive high-resolution melting (MS-HRM); genotyping was performed for MTHFR 677C&gt;T (rs1801133) and 1298A&gt;C (rs1801131), MTRR 66A&gt;G (rs1801394), MTR 2756A&gt;G (rs1805087), SLC19A1 (RFC1) 80G&gt;A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp ins\/del (rs34489327), DNMT3A -448A&gt;G (rs1550117), and DNMT3B -149C&gt;T (rs2424913) polymorphisms. We observed a statistically significant effect of the DNMT3B -149C&gt;T polymorphism on mean MTHFR methylation levels, and particularly CT and TT carriers showed increased methylation levels than CC carriers. The present study revealed an association between a functional polymorphism of DNMT3B and MTHFR methylation levels that could be of relevance in those disorders, such as inborn defects, metabolic disorders and cancer, that have been linked to impaired DNA methylation.<\/jats:p>","DOI":"10.3390\/ijms20153754","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T11:37:07Z","timestamp":1564573027000},"page":"3754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels"],"prefix":"10.3390","volume":"20","author":[{"given":"Fabio","family":"Copped\u00e8","sequence":"first","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6768-8466","authenticated-orcid":false,"given":"Andrea","family":"Stoccoro","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaola","family":"Tannorella","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"Doctoral School in Genetics, Oncology and Clinical Medicine, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Nicol\u00ec","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"Doctoral School in Genetics, Oncology and Clinical Medicine, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Migliore","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"ref_1","first-page":"6","article-title":"The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects","volume":"25","year":"2015","journal-title":"Front. 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