{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:35Z","timestamp":1787028575242,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82173608"],"award-info":[{"award-number":["82173608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404362"],"award-info":[{"award-number":["82404362"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preeclampsia (PE), a major cause of maternal and perinatal morbidity, is a hypertensive pregnancy disorder with poorly defined pathogenesis. While dysregulation of core circadian genes including brain and muscle ARNT-like 1 (BMAL1; also termed ARNTL) and circadian locomotor output cycles kaput (CLOCK) has been implicated in PE, the contribution of their genetic polymorphisms to PE remains unclear. In this case\u2013control study, polymorphisms in BMAL1 and CLOCK were genotyped using MassARRAY in 202 PE patients (97 early-onset [eoPE], 105 late-onset [loPE]) and 400 controls. Following genotyping and linkage disequilibrium-pruning (r2 &gt; 0.8) to retain representative tag SNPs, the final set for association analysis comprised three non-redundant BMAL1 SNPs (rs4757144, rs11022780, rs969485) and one CLOCK SNP (rs1048004). After confounder adjustment, no significant associations were detected for CLOCK variants, whereas the BMAL1 rs11022780 variant demonstrated a significant protective effect against PE (TT vs. CC: OR = 0.26 [95% CI 0.09\u20130.78]; recessive model: OR = 0.25 [95% CI 0.09\u20130.74]), particularly in the eoPE subgroup. Expression quantitative trait locus (eQTL) analysis confirmed that this SNP correlated with BMAL1 mRNA expression in whole blood, and protein\u2013protein interaction analysis highlighted BMAL1\u2032s central role in circadian networks, implying a genetically influenced regulatory mechanism of PE through BMAL1 expression.<\/jats:p>","DOI":"10.3390\/ijms262110797","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"10797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of BMAL1 and CLOCK Gene Polymorphisms with Preeclampsia Risk with Subtype Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2038-4530","authenticated-orcid":false,"given":"Fan","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiehua","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengshi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"},{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"},{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"},{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F1315","DOI":"10.1152\/ajprenal.00071.2020","article-title":"Preeclampsia beyond pregnancy: Long-term consequences for mother and child","volume":"318","author":"Turbeville","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S786","DOI":"10.1016\/j.ajog.2021.12.001","article-title":"Preeclampsia and eclampsia: The conceptual evolution of a syndrome","volume":"226","author":"Erez","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mar\u00edn, R., Chiarello, D.I., Abad, C., Rojas, D., Toledo, F., and Sobrevia, L. (2020). Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165961"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.preghy.2021.02.001","article-title":"Prevalence of hypertensive disorders in pregnancy in China: A systematic review and meta-analysis","volume":"24","author":"Li","year":"2021","journal-title":"Pregnancy Hypertens."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0140-6736(10)60279-6","article-title":"Pre-eclampsia","volume":"376","author":"Steegers","year":"2010","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Badagionis, M., Sergentanis, T.N., Pervanidou, P., Kalampokas, E., Vlahos, N., and Eleftheriades, M. (2022). Preeclampsia and Cerebral Palsy in Offspring. Children, 9.","DOI":"10.3390\/children9030385"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.preghy.2020.07.012","article-title":"Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies","volume":"22","author":"Ferreira","year":"2020","journal-title":"Pregnancy Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1161\/CIRCULATIONAHA.118.036748","article-title":"Cardiovascular Disease-Related Morbidity and Mortality in Women with a History of Pregnancy Complications","volume":"139","author":"Grandi","year":"2019","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/aogs.14523","article-title":"Pregnancy complications and later life women\u2019s health","volume":"102","author":"McNestry","year":"2023","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0140-6736(15)00070-7","article-title":"Pre-eclampsia","volume":"387","author":"Mol","year":"2016","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107.e1","DOI":"10.1016\/j.ajog.2018.04.002","article-title":"Long-term mortality risk and life expectancy following recurrent hypertensive disease of pregnancy","volume":"219","author":"Theilen","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ajog.2019.05.044","article-title":"Placental bed research: I. The placental bed: From spiral arteries remodeling to the great obstetrical syndromes","volume":"221","author":"Brosens","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0140-6736(20)31128-4","article-title":"The Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: An individual participant-level meta-analysis","volume":"396","author":"Bhutta","year":"2020","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1097\/CM9.0000000000001452","article-title":"Risk factors and maternal-fetal outcomes of pregnancies complicated by pre-eclampsia, following cesarean section after a trial vaginal birth","volume":"134","author":"Xu","year":"2021","journal-title":"Chin. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dimitriadis, E., Rolnik, D.L., Zhou, W., Estrada-Gutierrez, G., Koga, K., Francisco, R.P.V., Whitehead, C., Hyett, J., da Silva Costa, F., and Nicolaides, K. (2023). Pre-eclampsia. Nat. Rev. Dis. Primers, 9, Erratum in Nat. Rev. Dis. Primers 2023, 9, 35.","DOI":"10.1038\/s41572-023-00417-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/GCO.0000000000000419","article-title":"Cardiovascular origins of preeclampsia","volume":"29","author":"Kalafat","year":"2017","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kornacki, J., Olejniczak, O., Sibiak, R., Gutaj, P., and Wender-O\u017cegowska, E. (2023). Pathophysiology of Pre-Eclampsia-Two Theories of the Development of the Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010307"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d are associated with disorders of deep placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1469-7580.2008.01036.x","article-title":"Oxygen as modulator of trophoblast invasion","volume":"215","author":"Huppertz","year":"2009","journal-title":"J. Anat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1161\/HYPERTENSIONAHA.116.06421","article-title":"Angiogenic Factors in Preeclampsia: From Diagnosis to Therapy","volume":"67","author":"Karumanchi","year":"2016","journal-title":"Hypertension"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.preghy.2019.08.165","article-title":"Levels of syndecan-1 and hyaluronan in early- and late-onset preeclampsia","volume":"18","author":"Kornacki","year":"2019","journal-title":"Pregnancy Hypertens."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1172\/JCI17189","article-title":"Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia","volume":"111","author":"Maynard","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jri.2016.08.008","article-title":"Update of syncytiotrophoblast derived extracellular vesicles in normal pregnancy and preeclampsia","volume":"119","author":"Tannetta","year":"2017","journal-title":"J. Reprod. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Burton, G.J., Redman, C.W., Roberts, J.M., and Moffett, A. (2019). Pre-eclampsia: Pathophysiology and clinical implications. BMJ, 366.","DOI":"10.1136\/bmj.l2381"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1080\/14767058.2018.1427058","article-title":"The profiles of soluble adhesion molecules in the \u201cgreat obstetrical syndromes\u201d","volume":"32","author":"Docheva","year":"2019","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1056\/NEJMoa031884","article-title":"Circulating angiogenic factors and the risk of preeclampsia","volume":"350","author":"Levine","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.preghy.2021.12.003","article-title":"Clinical interpretation and implementation of the sFlt-1\/PlGF ratio in the prediction, diagnosis and management of preeclampsia","volume":"27","author":"Verlohren","year":"2022","journal-title":"Pregnancy Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"McLaughlin, K., Zhang, J., Lye, S.J., Parker, J.D., and Kingdom, J.C. (2018). Phenotypes of Pregnant Women Who Subsequently Develop Hypertension in Pregnancy. J. Am. Heart Assoc., 7.","DOI":"10.1161\/JAHA.118.009595"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1126\/science.1111726","article-title":"Latest advances in understanding preeclampsia","volume":"308","author":"Redman","year":"2005","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1161\/CIRCULATIONAHA.110.943407","article-title":"Hypertension in pregnancy and later cardiovascular risk: Common antecedents?","volume":"122","author":"Romundstad","year":"2010","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wu, P., Haththotuwa, R., Kwok, C.S., Babu, A., Kotronias, R.A., Rushton, C., Zaman, A., Fryer, A.A., Kadam, U., and Chew-Graham, C.A. (2017). Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis. Circ. Cardiovasc. Qual. Outcomes, 10.","DOI":"10.1161\/CIRCOUTCOMES.116.003497"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Boro\u0144, D., Kornacki, J., Gutaj, P., Mantaj, U., Wirstlein, P., and Wender-Ozegowska, E. (2022). Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus. J. Clin. Med., 12.","DOI":"10.3390\/jcm12010061"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1515\/jpm.2011.098","article-title":"Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia","volume":"39","author":"Ogge","year":"2011","journal-title":"J. Perinat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3109\/14767058.2011.591461","article-title":"Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion","volume":"25","author":"Soto","year":"2012","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Diallo, A.B., Coiffard, B., Desbriere, R., Katsogiannou, M., Donato, X., Bretelle, F., Mezouar, S., and Mege, J.L. (2023). Disruption of the Expression of the Placental Clock and Melatonin Genes in Preeclampsia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032363"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhou, G., Winn, E., Nguyen, D., Kasten, E.P., Petroff, M.G., and Hoffmann, H.M. (2022). Co-alterations of circadian clock gene transcripts in human placenta in preeclampsia. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22507-3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/SHK.0000000000001241","article-title":"Circadian Rhythm Disruption and Sepsis in Severe Trauma Patients","volume":"52","author":"Coiffard","year":"2019","journal-title":"Shock"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Diallo, A.B., Coiffard, B., Leone, M., Mezouar, S., and Mege, J.L. (2020). For Whom the Clock Ticks: Clinical Chronobiology for Infectious Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01457"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev-physiol-021909-135821","article-title":"The mammalian circadian timing system: Organization and coordination of central and peripheral clocks","volume":"72","author":"Dibner","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12576-018-0597-5","article-title":"The mammalian circadian system: A hierarchical multi-oscillator structure for generating circadian rhythm","volume":"68","author":"Honma","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.tibs.2022.04.009","article-title":"Time to target the circadian clock for drug discovery","volume":"47","author":"Rasmussen","year":"2022","journal-title":"Trends Biochem. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.tem.2016.03.015","article-title":"Circadian Metabolism: From Mechanisms to Metabolomics and Medicine","volume":"27","author":"Brown","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Clarkson-Townsend, D.A., Everson, T.M., Deyssenroth, M.A., Burt, A.A., Hermetz, K.E., Hao, K., Chen, J., and Marsit, C.J. (2019). Maternal circadian disruption is associated with variation in placental DNA methylation. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215745"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1177\/0748730417728671","article-title":"Rhythmic Three-Part Harmony: The Complex Interaction of Maternal, Placental and Fetal Circadian Systems","volume":"32","author":"Mark","year":"2017","journal-title":"J. Biol. Rhythm."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Miller, B.H., and Takahashi, J.S. (2013). Central circadian control of female reproductive function. Front. Endocrinol., 4.","DOI":"10.3389\/fendo.2013.00195"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3109\/19396368.2015.1069420","article-title":"Evidence for clock genes circadian rhythms in human full-term placenta","volume":"61","author":"Murias","year":"2015","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbrc.2008.11.006","article-title":"Evidence for circadian rhythms in human trophoblast cell line that persist in hypoxia","volume":"378","author":"Frigato","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/CIRCRESAHA.116.308034","article-title":"Circadian Influence on Metabolism and Inflammation in Atherosclerosis","volume":"119","author":"McAlpine","year":"2016","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23056","DOI":"10.18632\/oncotarget.8521","article-title":"Circadian factors BMAL1 and ROR\u03b1 control HIF-1\u03b1 transcriptional activity in nucleus pulposus cells: Implications in maintenance of intervertebral disc health","volume":"7","author":"Suyama","year":"2016","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.atherosclerosis.2018.05.046","article-title":"Loss of CLOCK under high glucose upregulates ROCK1-mediated endothelial to mesenchymal transition and aggravates plaque vulnerability","volume":"275","author":"Tang","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1172\/JCI76881","article-title":"Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation","volume":"125","author":"Xie","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1128\/MCB.01421-12","article-title":"Bmal1 and \u03b2-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced \u03b2-cell failure in mice","volume":"33","author":"Lee","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1101\/gad.237081.113","article-title":"The circadian clock regulates rhythmic activation of the NRF2\/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis","volume":"28","author":"Gibbs","year":"2014","journal-title":"Genes Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E2457","DOI":"10.1073\/pnas.1206274109","article-title":"Core circadian protein CLOCK is a positive regulator of NF-\u03baB-mediated transcription","volume":"109","author":"Spengler","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ye, L., Wu, H., and Xu, W. (2020). Deletion of Bmal1 Impairs Pancreatic \u03b2-Cell Function via Mitochondrial Signaling Pathway. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/9803024"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, Y., Li, J., Hou, Y., Huang, L., Bian, Y., Song, G., and Qiao, C. (2020). Circadian clock gene Clock is involved in the pathogenesis of preeclampsia through hypoxia. Life Sci., 247.","DOI":"10.1016\/j.lfs.2020.117441"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Min, Q., Hu, W., Lei, D., He, X., Liu, C., Li, Q., and Tian, W. (2024). The correlation of shift work and CLOCK, BMAL1, and PER1 gene polymorphisms with hypertension in healthcare workers: A cross-sectional study. Medicine, 103.","DOI":"10.1097\/MD.0000000000040148"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","article-title":"Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression","volume":"53","author":"Claringbould","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1096\/fj.12-205781","article-title":"The clock gene, brain and muscle Arnt-like 1, regulates adipogenesis via Wnt signaling pathway","volume":"26","author":"Guo","year":"2012","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/cbf.2871","article-title":"Over-expression of circadian clock gene Bmal1 affects proliferation and the canonical Wnt pathway in NIH-3T3 cells","volume":"31","author":"Lin","year":"2013","journal-title":"Cell Biochem. Funct."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chen, H., Chen, Y., and Zheng, Q. (2024). The regulated cell death at the maternal-fetal interface: Beneficial or detrimental?. Cell Death Discov., 10.","DOI":"10.1038\/s41420-024-01867-x"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1089\/ars.2021.0274","article-title":"Circadian Control of Mitochondria in Reactive Oxygen Species Homeostasis","volume":"37","author":"Mezhnina","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_64","first-page":"3150","article-title":"BMAL1 suppresses ROS-induced endothelial-to-mesenchymal transition and atherosclerosis plaque progression via BMP signaling","volume":"10","author":"Zhu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.yexcr.2017.07.029","article-title":"Impaired mitochondrial fusion, autophagy, biogenesis and dysregulated lipid metabolism is associated with preeclampsia","volume":"359","author":"Zhou","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nm.3599","article-title":"An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action","volume":"20","author":"Gibbs","year":"2014","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ebiom.2019.07.004","article-title":"Aryl hydrocarbon receptor nuclear translocator-like (ARNTL\/BMAL1) is associated with bevacizumab resistance in colorectal cancer via regulation of vascular endothelial growth factor A","volume":"45","author":"Burgermeister","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E8460","DOI":"10.1073\/pnas.1800431115","article-title":"Circadian clock protein BMAL1 regulates IL-1\u03b2 in macrophages via NRF2","volume":"115","author":"Early","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1093\/hmg\/ddx265","article-title":"Expression quantitative trait loci (eQTLs) in human placentas suggest developmental origins of complex diseases","volume":"26","author":"Peng","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"GTEx Consortium (2020). The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science, 369, 1318\u20131330.","DOI":"10.1126\/science.aaz1776"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.placenta.2012.03.008","article-title":"A rhythmic placenta? Circadian variation, clock genes and placental function","volume":"33","author":"Waddell","year":"2012","journal-title":"Placenta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1158\/0008-5472.CAN-09-3798","article-title":"CLOCK in breast tumorigenesis: Genetic, epigenetic, and transcriptional profiling analyses","volume":"70","author":"Hoffman","year":"2010","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Rahman, L., Anwar, R., and Mose, J.C. (2024). Maternal and neonatal outcome among women with early-onset preeclampsia and late-onset preeclampsia. Hypertens. Pregnancy, 43.","DOI":"10.1080\/10641955.2024.2405991"},{"key":"ref_74","unstructured":"Hypertensive Disorders in Pregnancy Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association (2020). Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: A clinical practice guideline in China (2020). Zhonghua Fu Chan Ke Za Zhi, 55, 227\u2013238."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1161\/HYPERTENSIONAHA.107.107607","article-title":"Placental origins of preeclampsia: Challenging the current hypothesis","volume":"51","author":"Huppertz","year":"2008","journal-title":"Hypertension"},{"key":"ref_76","first-page":"1","article-title":"The guidelines for prevention and control of overweight and obesity in Chinese adults","volume":"17","author":"Chen","year":"2004","journal-title":"Biomed. Environ. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: Analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10797\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T05:31:14Z","timestamp":1762579874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":77,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110797"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110797","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}