{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:08:06Z","timestamp":1770062886833,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,5,6]],"date-time":"2018-05-06T00:00:00Z","timestamp":1525564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472987"],"award-info":[{"award-number":["81472987"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773441"],"award-info":[{"award-number":["81773441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7162094"],"award-info":[{"award-number":["7162094"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD067244"],"award-info":[{"award-number":["HD067244"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD081216"],"award-info":[{"award-number":["HD081216"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD083809"],"award-info":[{"award-number":["HD083809"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,7,17]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Folate receptors (FRs) facilitate embryonic uptake of folates and are important for proper early embryonic development. There is accumulating evidence that blocking FR autoantibodies contribute to developmental diseases. However, genetic factors associated with the expression of FR autoantibodies remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated the effects of genetic polymorphisms in folate pathway genes on FR autoantibody titers in women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 302 pregnant women in China. The FR antigen\u2010down immunoassay was used to measure levels of FR autoantibodies including human immunoglobulin G (IgG) and immunoglobulin M (IgM) in maternal plasma. Genotypes were identified by matrix\u2010assisted laser desorption\/ionization time of flight mass spectrometry and polymerase chain reaction methods. General linear model was used to analyze the effects of genetic variants on FR autoantibody levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant associations were observed between genotypic variations and levels of FR autoantibodies. Plasma levels of FR autoantibodies in women with the TT genotype at <jats:italic>MTHFR<\/jats:italic> rs1801133 were significantly higher than those of women with the CC genotype (IgG: \u03b2\u2009=\u20090.62, 95% CI 0.21\u20131.04; IgM: \u03b2\u2009=\u20090.42, 95% CI 0.12\u20130.72). For <jats:italic>DNMT3A<\/jats:italic> rs7560488, the level of FR autoantibody IgG significantly increased in the TT genotype compared with CC genotype (\u03b2\u2009=\u20090.90, 95% CI 0.20\u20131.59). For <jats:italic>MTHFD2<\/jats:italic> rs828903, genotype GG was associated with elevated levels of FR autoantibody IgM compared to the AA genotype (\u03b2\u2009=\u20090.60, 95% CI 0.10\u20131.10). No association was detected between genetic variants of the <jats:italic>DHFR<\/jats:italic> gene with FR autoantibodies levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic variations in <jats:italic>MTHFR, DNMT3A<\/jats:italic>, and <jats:italic>MTHFD2<\/jats:italic> genes were associated with elevated plasma levels of FR autoantibodies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1334","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T06:35:55Z","timestamp":1525674955000},"page":"973-981","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene variants in the folate pathway are associated with increased levels of folate receptor autoantibodies"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-5062","authenticated-orcid":false,"given":"Yuqi","family":"Dong","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health, Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-9277","authenticated-orcid":false,"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunping","family":"Lei","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Biology and Medicine Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiguo","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health Peking University Health Science Center Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.08.104"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgo.2006.01.021"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der144"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2008.08.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2014.357"},{"issue":"1","key":"e_1_2_7_7_1","first-page":"19","article-title":"Understanding the immunobiology of pregnancy and applying it to treatment of recurrent pregnancy loss","volume":"4","author":"Coulam C. 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