{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T03:06:57Z","timestamp":1779246417507,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health System","doi-asserted-by":"crossref","award":["Lingjunrencai-02-02"],"award-info":[{"award-number":["Lingjunrencai-02-02"]}],"id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100019871","name":"Beijing Obstetrics and Gynecology Hospital, Capital Medical University","doi-asserted-by":"publisher","award":["FCYYJC202201"],"award-info":[{"award-number":["FCYYJC202201"]}],"id":[{"id":"10.13039\/501100019871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Research on folate levels in relation to hypertensive disorders of pregnancy (HDP) has yielded inconsistent results, often overlooking the roles of folic acid intake, genetic variations in folate metabolism, and DNA methylation. This study investigates the relationships among these factors and HDP risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A prospective cohort of 4079 Chinese pregnant women (2022\u20132024) assessed the association among folic acid intake, genetic polymorphisms, and red blood cell (RBC) folate metabolites, and gestational hypertension and preeclampsia. An epigenome-wide association study using UK Biobank data (231 057 women) identified folate-linked DNA methylation sites associated with HDP. Gestational hypertension was observed in 4.8% and preeclampsia in 4.4% of participants. Trajectories of low RBC 5-methyltetrahydrofolate during pregnancy were associated with a 57% increase in gestational hypertension risk (OR 1.57, 95% CI 1.15\u20132.15) compared to the median 5-methyltetrahydrofolate group. In contrast, high levels of unmetabolized and intermediary metabolites of folic acid in RBC were linked to a 101% increase in gestational hypertension risk (OR 2.01, 95% CI 1.27\u20133.17) relative to the low-level group. Pre-pregnancy folic acid intake was associated with elevated levels of 5-methyltetrahydrofolate and unmetabolized\/intermediary metabolites, and was linked to a reduced risk of gestational hypertension. Conversely, genetic variants associated with lower levels of 5-methyltetrahydrofolate and higher levels of unmetabolized\/intermediary metabolites were linked to an increased risk of gestational hypertension. The epigenome-wide association study identified two folate-related DNA methylation sites associated with HDP: cg16489826 (OR 1.28, 95% CI 1.12\u20131.47) and cg17054900 (OR 0.86, 95% CI 0.82\u20130.90).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre-pregnancy folic acid intake and genetic factors interact to be associated with HDP risk via folate metabolites, with differing relationships observed for 5-methyltetrahydrofolate and unmetabolized\/intermediary metabolites in gestational hypertension. Folate-related DNA methylation mechanisms may also be implicated in the risk of HDP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration No<\/jats:title>\n                    <jats:p>ChiCTR2400082398, ChiCTR2400090880<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>This study examines how folic acid intake, genetic variations, and folate metabolism are associated with the risk of hypertensive disorders during pregnancy, such as gestational hypertension and preeclampsia, while also identifying key DNA methylation sites associated with these conditions.Low levels of active folate (5-methyltetrahydrofolate) and high levels of unmetabolized\/intermediary metabolites in red blood cells during pregnancy are associated with a higher risk of gestational hypertension. Furthermore, folic acid intake and certain genetic variations may be linked to this risk through their association with the levels of metabolic byproducts.Two specific DNA methylation sites, cg16489826 and cg17054900, have been identified as associated with hypertensive disorders of pregnancy, highlighting a potential epigenetic connection between folate metabolism and these disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwag186","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:42:47Z","timestamp":1775216567000},"source":"Crossref","is-referenced-by-count":0,"title":["Folic acid intake, genetic variations, and DNA methylation in hypertensive disorders of pregnancy: a prospective cohort and epigenome-wide association study"],"prefix":"10.1093","author":[{"given":"Wei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Nutrition, Endocrinology and Metabolism, Beijing Obstetrics and Gynecology 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,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Endocrinology and Metabolism, Beijing Obstetrics and Gynecology Hospital, Capital Medical University , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]},{"name":"Beijing Maternal and Child Health Care Hospital , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianxian","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Endocrinology and Metabolism, Beijing Obstetrics and Gynecology Hospital, Capital Medical University , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]},{"name":"Beijing Maternal and Child Health Care Hospital , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Endocrinology and Metabolism, Beijing Obstetrics and Gynecology Hospital, Capital Medical University , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]},{"name":"Beijing Maternal and Child Health Care Hospital , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Endocrinology and Metabolism, Beijing Obstetrics and Gynecology Hospital, Capital Medical University , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 ,","place":["China"]},{"name":"Beijing Maternal and Child Health Care Hospital , No. 251 Yaojiayuan Road, Chaoyang District, Beijing 100026 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