{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:29:59Z","timestamp":1789846199663,"version":"4.0.1"},"reference-count":90,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":448,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["478652\/2010\u20130"],"award-info":[{"award-number":["478652\/2010\u20130"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008532","name":"Universidade Federal do Rio Grande do Norte","doi-asserted-by":"publisher","award":["397\/2020"],"award-info":[{"award-number":["397\/2020"]}],"id":[{"id":"10.13039\/501100008532","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014153","name":"Banco do Nordeste do Brasil","doi-asserted-by":"publisher","award":["912011"],"award-info":[{"award-number":["912011"]}],"id":[{"id":"10.13039\/501100014153","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mutation Research - Reviews in Mutation Research"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1016\/j.mrrev.2023.108470","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T08:57:16Z","timestamp":1694249836000},"page":"108470","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies"],"prefix":"10.1016","volume":"792","author":[{"given":"Carla Talita Azevedo","family":"Ginani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson Rom\u00e1ryo Duarte","family":"da Luz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kleyton Santos","family":"de Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayane Cristine Alves","family":"Sarmento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Copped\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-0922","authenticated-orcid":false,"given":"Maria","family":"das Gra\u00e7as Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mrrev.2023.108470_bib1","first-page":"6","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"10.1016\/j.mrrev.2023.108470_bib2","first-page":"1","article-title":"Altered folate homeostasis in children with down syndrome: a potential basis for enhanced methotrexate toxicity","author":"Funk","year":"2020","journal-title":"J. Pedia"},{"key":"10.1016\/j.mrrev.2023.108470_bib3","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1007\/s00204-016-1843-3","article-title":"Risk factors for Down syndrome","volume":"90","author":"Copped\u00e8","year":"2016","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.mrrev.2023.108470_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.mrrev.2020.108320","article-title":"Mechanisms of oocyte aneuploidy associated with advanced maternal age","volume":"785","author":"Mikwar","year":"2020","journal-title":"Mutat. Res. \/Rev. Mutat. Res."},{"key":"10.1016\/j.mrrev.2023.108470_bib5","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1007\/s00018-016-2276-0","article-title":"Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility","volume":"73","author":"Jackson","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.mrrev.2023.108470_bib6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1017\/S0016672310000224","article-title":"Chromosome 21 non-disjunction and Down syndrome birth in an Indian cohort: analysis of incidence and aetiology from family linkage data","volume":"92","author":"Ghosh","year":"2010","journal-title":"Genet Res"},{"key":"10.1016\/j.mrrev.2023.108470_bib7","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/ajcn\/70.4.495","article-title":"Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome","volume":"70","author":"James","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.mrrev.2023.108470_bib8","first-page":"555","article-title":"Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for down syndrome offspring: A meta-analysis","volume":"68","author":"Wu","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"10.1016\/j.mrrev.2023.108470_bib9","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/cga.12232","article-title":"Genetic polymorphisms and folate status","volume":"57","author":"Hiraoka","year":"2017","journal-title":"Congenit. Anom."},{"key":"10.1016\/j.mrrev.2023.108470_bib10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mrrev.2009.06.001","article-title":"The complex relationship between folate\/homocysteine metabolism and risk of Down syndrome","volume":"682","author":"Copped\u00e8","year":"2009","journal-title":"Mutat. Res"},{"key":"10.1016\/j.mrrev.2023.108470_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2015.00223","article-title":"The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects","volume":"6","author":"Copped\u00e8","year":"2015","journal-title":"Front Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0165-6147(00)01675-8","article-title":"Biological and clinical implications of the MTHFR C677T polymorphism","volume":"22","author":"Ueland","year":"2001","journal-title":"Trends Pharm. Sci."},{"key":"10.1016\/j.mrrev.2023.108470_bib13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/mgme.1998.2714","article-title":"A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity","volume":"64","author":"Weisberg","year":"1998","journal-title":"Mol. Genet Metab."},{"key":"10.1016\/j.mrrev.2023.108470_bib14","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1080\/10408398.2013.807221","article-title":"Application of the key events dose-response framework to folate metabolism","volume":"56","author":"Hu","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"10.1016\/j.mrrev.2023.108470_bib15","first-page":"1","article-title":"MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: A meta-analysis from 16 case-control studies","volume":"43","author":"Yu","year":"2017","journal-title":"Ital. J. Pedia"},{"key":"10.1016\/j.mrrev.2023.108470_bib16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00439-006-0290-2","article-title":"Functional inference of the methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms from a large-scale epidemiological study","volume":"121","author":"Ulvik","year":"2007","journal-title":"Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib17","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s11033-012-2270-z","article-title":"Association of methylenetetrahydrofolate reductase gene 677C>T polymorphism and Down Syndrome","volume":"40","author":"Costa-Lima","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.mrrev.2023.108470_bib18","first-page":"372","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"71","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1016\/j.mrrev.2023.108470_bib19","unstructured":"G.A. Wells, B. Shea, D. O\u2019Connell, J. Peterson, V. Welch, M. Losos, P. Tugwell, The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. \u3008https:\/\/www.ohri.ca\/\/programs\/clinical_epidemiology\/oxford.Asp\u3009. Print 2022 Jun."},{"key":"10.1016\/j.mrrev.2023.108470_bib20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2307\/3001666","article-title":"The combination of estimates from diferente experiments","volume":"10","author":"Cochran","year":"1954","journal-title":"Biometrics"},{"key":"10.1016\/j.mrrev.2023.108470_bib21","first-page":"719","article-title":"Statistical aspects of the analysis of data from retrospective studies of disease","volume":"22","author":"Mantel","year":"1959","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.mrrev.2023.108470_bib22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin. Trials"},{"key":"10.1016\/j.mrrev.2023.108470_bib23","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med"},{"key":"10.1016\/j.mrrev.2023.108470_bib24","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"key":"10.1016\/j.mrrev.2023.108470_bib25","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"10.1016\/j.mrrev.2023.108470_bib26","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/jnci\/djh075","article-title":"Assessing the probability that a positive report is false: An approach for molecular epidemiology studies","volume":"96","author":"Wacholder","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.mrrev.2023.108470_bib27","first-page":"551","article-title":"Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis","volume":"66","author":"Yang","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"10.1016\/j.mrrev.2023.108470_bib28","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1086\/303055","article-title":"Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome","volume":"67","author":"Hobbs","year":"2000","journal-title":"Am. J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/ajmg.10121","article-title":"MTRR and MTHFR polymorphism: Link to Down syndrome?","volume":"107","author":"O\u2019Leary","year":"2002","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib30","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1203\/00006450-200206000-00018","article-title":"Methylenetetrahydrofolate reductase polymorphism in the etiology of down syndrome","volume":"51","author":"Chadefaux-Vekemans","year":"2002","journal-title":"Pedia Res"},{"key":"10.1016\/j.mrrev.2023.108470_bib31","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/sj.ejhg.5200819","article-title":"C677T mutation in the 5,10-MTHFR gene and risk of Down syndrome in Italy","volume":"10","author":"Stuppia","year":"2002","journal-title":"Eur. J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/ajmg.a.20234","article-title":"Methionine synthase (MTR) 2756 (A\u2192G) polymorphism, double heterozygosity methionine synthase 2756 AG\/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are three risk factors for having a child with down syndrome","volume":"121A","author":"Bosco","year":"2003","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/ajmg.a.20432","article-title":"Methylenetetrahydrofolate reductase enzyme polymorphisms as maternal risk for Down syndrome among Turkish women","volume":"127","author":"Boduro\u01e7lu","year":"2004","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib34","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ajmg.a.30591","article-title":"Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in Brazil","volume":"135","author":"Da Silva","year":"2005","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1079\/BJN20051490","article-title":"No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down\u2019s syndrome among French mothers","volume":"94","author":"Chango","year":"2005","journal-title":"Br. J. Nutr."},{"key":"10.1016\/j.mrrev.2023.108470_bib36","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/pd.1296","article-title":"Methylenetetrahydrofolate reductase gene polymorphisms and their association with trisomy 21","volume":"13","author":"Ac\u00e1cio","year":"2005","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.mrrev.2023.108470_bib37","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s10038-005-0356-3","article-title":"MTHFR C677T and A1298C polymorphisms are risk factors for Down\u2019s syndrome in Indian mothers","volume":"51","author":"Rai","year":"2006","journal-title":"J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib38","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/ajmg.a.31217","article-title":"Folate gene polymorphisms and the risk of Down syndrome pregnancies in young Italian women","volume":"140A","author":"Copped\u00e8","year":"2006","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib39","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/01.gim.0000228206.21793.82","article-title":"Analysis of seven maternal polymorphisms of genes involved in homocysteine\/folate metabolism and risk of Down syndrome offspring","volume":"8","author":"Scala","year":"2006","journal-title":"Genet Med"},{"key":"10.1016\/j.mrrev.2023.108470_bib40","first-page":"533","article-title":"The relationship between polymorphism of gene involved in folate metabolism, homocysteine level and risk of Down syndrome, Chinese","volume":"24","author":"Wang","year":"2007","journal-title":"J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1155\/2008\/214027","article-title":"MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down syndrome children","volume":"24","author":"Meguid","year":"2008","journal-title":"Dis. Markers"},{"key":"10.1016\/j.mrrev.2023.108470_bib42","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1002\/ajmg.a.32308","article-title":"The biochemical structure and function of methylenetetrahydrofolate reductase provide the rationale to interpret the epidemiological results on the risk for infants with Down syndrome","volume":"146A","author":"Mart\u00ednez-Fr\u00edas","year":"2008","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1631\/jzus.B0710599","article-title":"Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China","volume":"9","author":"Wang","year":"2008","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"10.1016\/j.mrrev.2023.108470_bib44","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3104\/reports.2004","article-title":"Prevalence of MTHFR C677T polymorphism in north Indian mothers having babies with Trisomy 21 Down syndrome","volume":"12","author":"Kohli","year":"2008","journal-title":"Downs Syndr. Res Pr."},{"key":"10.1016\/j.mrrev.2023.108470_bib45","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1155\/2008\/487023","article-title":"The impact of folate pathway polymorphisms combined to nutritional deficiency as a maternal predisposition factor for Down syndrome","volume":"25","author":"Santos-Rebou\u00e7as","year":"2008","journal-title":"Dis. Markers"},{"key":"10.1016\/j.mrrev.2023.108470_bib46","doi-asserted-by":"crossref","first-page":"636.e1","DOI":"10.1016\/j.ajog.2008.12.046","article-title":"Maternal polymorphisms for methyltetrahydrofolate reductase and methionine synthetase reductase and risk of children with Down syndrome","volume":"200","author":"Pozzi","year":"2009","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.mrrev.2023.108470_bib47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neulet.2008.10.074","article-title":"Association of maternal polymorphisms in folate metabolizing genes with chromosome damage and risk of Down syndrome offspring","volume":"449","author":"Copped\u00e8","year":"2009","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.mrrev.2023.108470_bib48","first-page":"15","article-title":"MTHFR gene variants C677T, A1298C and association with Down syndrome: a case-control study from South India","volume":"15","author":"Cyril","year":"2009","journal-title":"Indian J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib49","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1002\/ajmg.a.32989","article-title":"Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects","volume":"149","author":"Brandalize","year":"2009","journal-title":"Am. J. Med Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib50","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3724\/SP.J.1005.2010.00461","article-title":"Folate gene polymorphism and the risk of Down syndrome pregnancies in young Chinese women","volume":"32","author":"Ya-Ping","year":"2010","journal-title":"Yi Chuan"},{"key":"10.1016\/j.mrrev.2023.108470_bib51","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1155\/2010\/216046","article-title":"Functional inference of methylenetetrahydrofolate reductase gene polymorphisms on enzyme stability as a potential risk factor for Down syndrome in Croatia","volume":"28","author":"Vranekovi\u0107","year":"2010","journal-title":"Dis. Markers"},{"key":"10.1016\/j.mrrev.2023.108470_bib52","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1089\/gtmb.2010.0057","article-title":"Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C as maternal risk factors for Down syndrome in Jordan","volume":"15","author":"Sadiq","year":"2011","journal-title":"Genet Test. Mol. Biomark."},{"key":"10.1016\/j.mrrev.2023.108470_bib53","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1155\/2012\/693864","article-title":"Maternal risk for Down Syndrome is modulated by genes involved in folate metabolism","volume":"32","author":"Zampieri","year":"2012","journal-title":"Dis. Markers"},{"key":"10.1016\/j.mrrev.2023.108470_bib54","doi-asserted-by":"crossref","first-page":"285","DOI":"10.4103\/0971-6866.107977","article-title":"Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down Syndrome","volume":"18","author":"Mohanty","year":"2012","journal-title":"Indian J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib55","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejmhg.2012.04.003","article-title":"The methylenetetrahydrofolate reductase gene variant (C677T) in risk mothers with Down syndrome among Saudi population","volume":"13","author":"Tayeb","year":"2012","journal-title":"Egypt J. Med Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib56","doi-asserted-by":"crossref","first-page":"412","DOI":"10.4103\/0971-6866.124368","article-title":"Prevalence of methylenetetrahydrofolate reductase 677C-T polymorphism among mothers of Down syndrome children","volume":"19","author":"Kaur","year":"2013","journal-title":"Indian J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib57","first-page":"B249","article-title":"Genetic polymorphisms of MTHFR (677T and 1298C) and homocysteine metabolism as maternal risk factor for down\u2019s syndrome patients in north Indian population","volume":"4","author":"Pandey","year":"2013","journal-title":"Int J. Pharma Bio Sci."},{"key":"10.1016\/j.mrrev.2023.108470_bib58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejmhg.2013.09.003","article-title":"Maternal MTHFR C677T genotype and septal defects in offspring with Down Syndrome: A pilot study","volume":"15","author":"Elsayed","year":"2014","journal-title":"Egypt J. Med Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib59","first-page":"1","article-title":"Altered LINE-1 methylation in mothers of children with Down Syndrome","volume":"10","author":"Bozovi\u0107","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.mrrev.2023.108470_bib60","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1089\/gtmb.2014.0262","article-title":"Folate metabolism gene polymorphisms and risk for Down syndrome offspring in turkish women","volume":"19","author":"Ay","year":"2015","journal-title":"Genet Test. Mol. Biomark."},{"key":"10.1016\/j.mrrev.2023.108470_bib61","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1093\/humrep\/dev126","article-title":"Role of folate-homocysteine pathway gene polymorphisms and nutritional cofactors in Down Syndrome: A triad study","volume":"30","author":"Sukla","year":"2015","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.mrrev.2023.108470_bib62","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejmhg.2015.08.003","article-title":"Do the MTHFR gene polymorphism and Down Syndrome pregnancy association stands true? A case-control study of Indian population and meta-analysis","volume":"17","author":"Muthuswamy","year":"2016","journal-title":"Egypt J. Med Hum. Genet."},{"key":"10.1016\/j.mrrev.2023.108470_bib63","first-page":"1","article-title":"Screening of six polymorphisms related with folate metabolism in parents of individuals with Down syndrome","author":"Balarin","year":"2017","journal-title":"J. Matern Neonatal Med."},{"key":"10.1016\/j.mrrev.2023.108470_bib64","first-page":"27","article-title":"Polimorfismul C677T si A1298C al genei MTHFR ca factor de risc matern pentru trisomia 21 (Studiu monocentric)","volume":"25","author":"Bucerzan","year":"2017","journal-title":"Rev. Rom. Med Lab."},{"key":"10.1016\/j.mrrev.2023.108470_bib65","doi-asserted-by":"crossref","first-page":"73","DOI":"10.17826\/cumj.340356","article-title":"T\u00fcrk populasyonunda maternal MTHFR geni polimorfizmleri ve Down sendromlu \u00e7ocuk sahibi olma riski","volume":"43","author":"Keser","year":"2018","journal-title":"Cukurova Med J."},{"key":"10.1016\/j.mrrev.2023.108470_bib66","doi-asserted-by":"crossref","DOI":"10.1016\/j.mgene.2019.100606","article-title":"Polymorphisms of folate metabolism regulators increase risk of meiosis II nondisjunction of chromosome 21 in oocyte","volume":"22","author":"Halder","year":"2019","journal-title":"Meta Gene"},{"key":"10.1016\/j.mrrev.2023.108470_bib67","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1080\/14767058.2018.1424818","article-title":"Genetic polymorphisms in folate metabolism as risk for Down syndrome in the southern China","volume":"32","author":"Jiajin","year":"2019","journal-title":"J. Matern Neonatal Med."},{"key":"10.1016\/j.mrrev.2023.108470_bib68","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s43042-019-0010-9","article-title":"MTHFR gene polymorphism and associated nutritional deficiency in the etiology and pathogenesis of Down syndrome","volume":"20","author":"Kedar","year":"2019","journal-title":"Egypt J. Med Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib69","doi-asserted-by":"crossref","first-page":"251","DOI":"10.17219\/acem\/115078","article-title":"Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down Syndrome) in a Polish population","volume":"29","author":"Czechowicz","year":"2020","journal-title":"Adv. Clin. Exp. Med"},{"key":"10.1016\/j.mrrev.2023.108470_bib70","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4103\/tcmj.tcmj_258_21","article-title":"Role of folate metabolizing genes and homocysteine in mothers of Down syndrome children","volume":"34","author":"Kaur","year":"2022","journal-title":"Tzu Chi Med J."},{"key":"10.1016\/j.mrrev.2023.108470_bib71","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.mrfmmm.2004.03.008","article-title":"Folate deficiency induces aneuploidy in human lymphocytes in vitro-evidence using cytokinesis-blocked cells and probes specific for chromosomes 17 and 21","volume":"551","author":"Wang","year":"2004","journal-title":"Mutat. Res."},{"key":"10.1016\/j.mrrev.2023.108470_bib72","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1002\/ajmg.a.31886","article-title":"Polymorphisms in folate and homocysteine metabolizing genes and chromosome damage in mothers of Down syndrome children","volume":"143A","author":"Copped\u00e8","year":"2007","journal-title":"Am. J. Med Genet A"},{"key":"10.1016\/j.mrrev.2023.108470_bib73","first-page":"3","article-title":"Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks","volume":"24","author":"Copped\u00e8","year":"2010","journal-title":"BMC Med Genom."},{"key":"10.1016\/j.mrrev.2023.108470_bib74","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3390\/ijms22020639","article-title":"Fission Yeast Methylenetetrahydrofolate Reductase Ensures Mitotic and Meiotic Chromosome Segregation Fidelity","volume":"22","author":"Lim","year":"2021","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.mrrev.2023.108470_bib75","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s10038-007-0202-x","article-title":"Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis","volume":"52","author":"Zintzaras","year":"2007","journal-title":"J. Hum. Genet"},{"key":"10.1016\/j.mrrev.2023.108470_bib76","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejogrb.2012.11.022","article-title":"Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for Down syndrome offspring: a meta-analysis","volume":"167","author":"Wu","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"10.1016\/j.mrrev.2023.108470_bib77","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/mutage\/get045","article-title":"Maternal gene polymorphisms involved in folate metabolism and the risk of having a down syndrome offspring: A meta-analysis","volume":"28","author":"Yang","year":"2013","journal-title":"Mutagenesis"},{"key":"10.1016\/j.mrrev.2023.108470_bib78","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1007\/s11033-014-3424-y","article-title":"Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: Increased susceptibility in women carriers of the MTHFR 677T allele","volume":"41","author":"Victorino","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.mrrev.2023.108470_bib79","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108552","article-title":"Maternal methylenetetrahydrofolate reductase C677T polymorphism and down syndrome risk: a meta-analysis from 34 studies","volume":"9","author":"Rai","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.mrrev.2023.108470_bib80","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/pd.5396","article-title":"The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes","volume":"39","author":"Zhang","year":"2019","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.mrrev.2023.108470_bib81","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.gene.2013.09.063","article-title":"Folate: Metabolism, genes, polymorphisms and the associated diseases","volume":"533","author":"Nazki","year":"2014","journal-title":"Gene"},{"key":"10.1016\/j.mrrev.2023.108470_bib82","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1007\/s13577-021-00586-0","article-title":"One-carbon metabolism and global DNA methylation in mothers of individuals with Down syndrome","volume":"34","author":"Mendes","year":"2021","journal-title":"Hum. Cell"},{"key":"10.1016\/j.mrrev.2023.108470_bib83","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/pd.6214","article-title":"Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy","volume":"42","author":"Miljanovi\u0107","year":"2022","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.mrrev.2023.108470_bib84","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.fertnstert.2012.12.027","article-title":"Association of maternal and fetal MTHFR A1298C polymorphism with the risk of pregnancy loss: a study of an Indian population and a meta-analysis","volume":"99","author":"Nair","year":"2013","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.mrrev.2023.108470_bib85","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1741-4520.2011.00350.x","article-title":"Molecular basis of maternal age-related increase in oocyte aneuploidy","volume":"52","author":"Kurahashi","year":"2012","journal-title":"Congenit. Anom."},{"key":"10.1016\/j.mrrev.2023.108470_bib86","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1159\/000515121","article-title":"Methylenetetrahydrofolate Reductase Dimer Configuration as a Risk Factor for Maternal Meiosis I-Derived Trisomy 21","volume":"85","author":"Vranekovi\u0107","year":"2020","journal-title":"Hum. Hered."},{"key":"10.1016\/j.mrrev.2023.108470_bib87","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/gepi.20518","article-title":"Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome","volume":"34","author":"Locke","year":"2010","journal-title":"Genet Epidemiol."},{"key":"10.1016\/j.mrrev.2023.108470_bib88","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1442-200X.2010.03310.x","article-title":"MTHFR C677T and A1298C polymorphisms as a risk factor for congenital heart defects in Down syndrome","volume":"53","author":"Bo\u017eovi\u0107","year":"2011","journal-title":"Pedia Int"},{"key":"10.1016\/j.mrrev.2023.108470_bib89","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.3390\/nu9121288","article-title":"Adult nutrient intakes from current national dietary surveys of european populations","volume":"9","author":"Rippin","year":"2017","journal-title":"Nutrients"},{"key":"10.1016\/j.mrrev.2023.108470_bib90","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ejogrb.2022.10.010","article-title":"Folic acid fortification of flour to prevent neural tube defects in Europe - A position statement by the European Board and college of obstetrics and gynaecology (EBCOG)","author":"Petch","year":"2022","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."}],"container-title":["Mutation Research - Reviews in Mutation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1383574223000182?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1383574223000182?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T11:57:35Z","timestamp":1736423855000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1383574223000182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":90,"alternative-id":["S1383574223000182"],"URL":"https:\/\/doi.org\/10.1016\/j.mrrev.2023.108470","relation":{},"ISSN":["1383-5742"],"issn-type":[{"value":"1383-5742","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies","name":"articletitle","label":"Article Title"},{"value":"Mutation Research - Reviews in Mutation Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mrrev.2023.108470","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"108470"}}