{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T13:55:24Z","timestamp":1781358924647,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Preeclampsia (PE) is a complex pregnancy disorder associated with early placental hypoxia, oxidative stress, and impaired angiogenic signaling. Melatonin and soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK) contribute to antioxidant and vascular pathways, whereas their receptors, melatonin receptor 1A (\n MTNR1A<\/jats:italic>\n ), melatonin receptor 1B (\n MTNR1B<\/jats:italic>\n ), and fibroblast growth factor\u2010inducible 14 (\n Fn14)<\/jats:italic>\n , may be subject to epigenetic regulation. This study assessed serum melatonin and sTWEAK levels in parallel with promoter methylation of\n MTNR1A<\/jats:italic>\n ,\n MTNR1B<\/jats:italic>\n , and\n Fn14<\/jats:italic>\n in early gestation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A mixed design cohort was recruited between 13 and 20 weeks of gestation. A total of 198 pregnant women were categorized as pregnant control, high risk, or preeclamptic at enrollment time. Serum melatonin and sTWEAK were measured by enzyme\u2010linked immunosorbent assay (ELISA). Promoter methylation of\n MTNR1A<\/jats:italic>\n ,\n MTNR1B<\/jats:italic>\n , and\n Fn14<\/jats:italic>\n was assessed using methylation\u2010specific PCR with semi quantitative densitometry.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum sTWEAK levels were significantly lower in high\u2010risk and preeclamptic women, whereas melatonin levels showed a downward trend without reaching statistical significance. Promoter methylation of\n MTNR1A<\/jats:italic>\n and\n Fn14<\/jats:italic>\n was elevated in both high\u2010risk and preeclamptic groups, whereas\n MTNR1B<\/jats:italic>\n showed no notable differences. Multivariate analysis revealed that lower sTWEAK (OR 0.837; 95% confidence interval [CI] 0.782\u20130.896;\n p<\/jats:italic>\n \u00a0<\u00a00.001) and higher\n Fn14<\/jats:italic>\n methylation (OR 0.935; 95% CI 0.882\u20130.992;\n p<\/jats:italic>\n \u00a0=\u00a00.027) were independently associated with hypertensive outcomes.\u00a0 Additionally, higher\n Fn14<\/jats:italic>\n methylation in early pregnancy was observed in high\u2010risk women who later developed hypertensive disorders.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Early pregnancy hypermethylation of\n MTNR1A<\/jats:italic>\n and\n Fn14, but not MTNR1B<\/jats:italic>\n , was observed in high\u2010risk and PE women and co\u2010occurred with a significantly reduced sTWEAK level and non\u2010significantly reduced serum melatonin, suggesting epigenetic modulation of antioxidant and angiogenic pathways in women at risk for PE. These findings establish associations rather than causation and require validation using quantitative assays in multicenter cohorts before clinical translation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ahg.70042","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:09:19Z","timestamp":1780924159000},"page":"256-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Shifts in\n MTNR1A, MTNR1B<\/i>\n and\n Fn14<\/i>\n and Their Links to Preeclampsia Risk"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1590-5956","authenticated-orcid":false,"given":"Sana Kashif","family":"Shahid","sequence":"first","affiliation":[{"name":"Department of Physiology, Fazaia Ruth Pfau Medical College Air University Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-0225","authenticated-orcid":false,"given":"Syeda Sadia","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6017-3953","authenticated-orcid":false,"given":"Sabah","family":"Farhat","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Aga Khan University Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-472X","authenticated-orcid":false,"given":"Shah Jabeen","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Fazaia Ruth Pfau Medical College Air University Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-8877","authenticated-orcid":false,"given":"Mehir un Nisa","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Karachi Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy.2013.Hypertension in Pregnancy.ACOG."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112837"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10071020"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12111560"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.14356"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-020-00313-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2020.09.004"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061307"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/10641955.2019.1581215"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.52547\/ijrr.19.4.12"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2023.2282100"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-018-2799-3"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-025-00696-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1339304"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14081903"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-023-04661-y"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.7.1713"},{"issue":"11","key":"e_1_2_12_19_1","article-title":"Preeclampsia Incidence and Its Maternal and Neonatal Outcomes With Associated Risk Factors","volume":"14","author":"Khan B.","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000444524"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00058.2023"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz287"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2023.111776"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/09612033221141261"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061155"},{"issue":"16","key":"e_1_2_12_26_1","first-page":"3899","article-title":"Quantitative Analysis of Aberrant p16 Methylation Using Real\u2010Time Quantitative Methylation\u2010Specific Polymerase Chain Reaction","volume":"59","author":"Lo Y. 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