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Previously, it has been shown that the common\n                    <jats:italic>C.677C &gt; T<\/jats:italic>\n                    polymorphism in\n                    <jats:italic>MTHFR<\/jats:italic>\n                    influences global DNA methylation status through a direct interaction with folate status and (indirectly) with total homocysteine (tHcy) levels. To build on that and other more recent observations that have further highlighted associations among\n                    <jats:italic>MTHFR C.677C &gt; T<\/jats:italic>\n                    , tHcy, and aberrations in DNA methylation, we investigated whether the interaction between mildly elevated plasma tHcy and the\n                    <jats:italic>C.677C &gt; T<\/jats:italic>\n                    polymorphism is associated with site\u2010specific changes in DNA methylation in humans. We used data on plasma tHcy levels,\n                    <jats:italic>c.677C&gt; T<\/jats:italic>\n                    polymorphism, and site\u2010specific DNA methylation levels for a total of 915 white women and 335 men from the TwinsUK registry (\n                    <jats:italic>n<\/jats:italic>\n                    = 610) and the Rotterdam study (\n                    <jats:italic>n<\/jats:italic>\n                    = 670). We performed methylome\u2010wide association analyses in each cohort to model the interaction between levels of tHcy and\n                    <jats:italic>C.677C &gt; T<\/jats:italic>\n                    genotypes on DNA methylation \u03b2 values. Our meta\u2010analysis identified 13 probes significantly associated with\n                    <jats:italic>rs1801133 \u00d7<\/jats:italic>\n                    tHcy levels [false\u2010discovery rate (FDR) &lt; 0.05]. The most significant associations were with a cluster of probes at the\n                    <jats:italic>AGTRAP\u2013MTHFR\u2013NPPA\/B<\/jats:italic>\n                    gene locus on chromosome 1 (FDR = 1.3E\u201304), with additional probes on chromosomes 2, 3, 4, 7, 12, 16, and 19. Our top 2 hits on chromosome 1 were functionally associated with variability in expression of the TNF receptor superfamily member 8 (\n                    <jats:italic>TNFRSF8<\/jats:italic>\n                    ) gene\/locus on that chromosome. This is the first study, to our knowledge, to provide a direct link between perturbations in 1\u2010carbon metabolism, through an interaction of tHcy and the activity of MTHFR enzyme on epigenetic regulation of the genome\n                    <jats:italic>via<\/jats:italic>\n                    DNA methylation.\u2014Nash, A. J., Mandaviya, P. R., Dib, M.\u2010J., Uitterlinden, A. G., van Meurs, J., Heil, S. G., Andrew, T., Ahmadi, K. R. Interaction between plasma homocysteine and the MTHFR c.677C&gt;T polymorphism is associated with site\u2010specific changes in DNA methylation in humans. FASEB J. 33, 833\u2013843 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800400r","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T16:58:56Z","timestamp":1533574736000},"page":"833-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interaction between plasma homocysteine and the\n                    <i>MTHFR C.677C &gt; T<\/i>\n                    polymorphism is associated with site\u2010specific changes in DNA methylation in humans"],"prefix":"10.1096","volume":"33","author":[{"given":"Alexander J.","family":"Nash","sequence":"first","affiliation":[{"name":"Institute of Clinical Sciences Medical Research Council (MRC) London Institute of Medical Sciences  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja R.","family":"Mandaviya","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Erasmus University Medical Center  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Joe","family":"Dib","sequence":"additional","affiliation":[{"name":"Department of Genomics of Common Disease Imperial College  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 G.","family":"Uitterlinden","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van Meurs","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus 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