{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:08:00Z","timestamp":1775711280144,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,6,11]],"date-time":"2010-06-11T00:00:00Z","timestamp":1276214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Low folate and high homocysteine (Hcy) concentrations are associated with pregnancy\u2010related pathologies such as spina bifida. Polymorphisms in folate\/Hcy metabolic enzymes may contribute to this potentially pathogenic biochemical phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The study comprised 26 Caucasian and 23 African\u2010American premenopausal women. Subjects gave fasting blood samples for biochemical phenotyping and genotyping. Total Hcy (tHcy) and both plasma and red blood cell (RBC) folate derivatives (i.e. tetrahydrofolate [THF], 5\u2010methylTHF [5\u2010MTHF], and 5,10\u2010methenylTHF [5,10\u2010MTHF]) were measured using stable isotope dilution liquid chromatography, multiple reaction monitoring, and mass spectrometry. Eleven polymorphisms from nine folate\/Hcy pathway genes were genotyped. Tests of association between genetic, lifestyle, and biochemical variables were applied.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In African American women, tHcy concentrations were associated (<jats:italic>p<\/jats:italic> &lt; 0.05) with total RBC folate, RBC 5\u2010MTHF, B<jats:sub>12<\/jats:sub>, and polymorphisms in <jats:italic>methionine synthase<\/jats:italic> (<jats:italic>MTR<\/jats:italic>) and <jats:italic>thymidylate synthase<\/jats:italic> (<jats:italic>TYMS<\/jats:italic>). In Caucasian women, tHcy concentrations were not associated with total folate levels, but were associated (<jats:italic>p<\/jats:italic> &lt; 0.05) with RBC THF, ratios of RBC 5\u2010MTHF:THF, and polymorphisms in <jats:italic>5,10\u2010methylenetetrahydrofolate reductase<\/jats:italic> (<jats:italic>MTHFR<\/jats:italic>) and <jats:italic>MTR<\/jats:italic>. In African Americans, folate derivative levels were associated with smoking, B<jats:sub>12<\/jats:sub>, and polymorphisms in <jats:italic>MTR<\/jats:italic>, <jats:italic>TYMS<\/jats:italic>, <jats:italic>methionine synthase reductase<\/jats:italic> (<jats:italic>MTRR<\/jats:italic>), and <jats:italic>reduced folate carrier1<\/jats:italic> (<jats:italic>RFC1<\/jats:italic>). In Caucasians, folate derivative levels were associated with vitamin use, B<jats:sub>12<\/jats:sub>, and polymorphisms in <jats:italic>MTHFR<\/jats:italic>, <jats:italic>TYMS<\/jats:italic>, and <jats:italic>RFC1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Polymorphisms in the folate\/Hcy pathway are associated with tHcy and folate derivative levels. In African American and Caucasian women, different factors are associated with folate\/Hcy phenotypes and may contribute to race\u2010specific differences in the risks of a range of pregnancy\u2010related pathologies. Birth Defects Research (Part A), 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20683","type":"journal-article","created":{"date-parts":[[2010,6,11]],"date-time":"2010-06-11T18:41:36Z","timestamp":1276281696000},"page":"679-688","source":"Crossref","is-referenced-by-count":16,"title":["Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women"],"prefix":"10.1002","volume":"88","author":[{"given":"Carolyn M.","family":"Summers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Stanislawska\u2010Sachadyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley F.","family":"Baido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan M.","family":"Von Feldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S.","family":"Whitehead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,8,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.13217"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412001"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010290"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/344213"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-1039-9"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.01.023"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000061"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00469-X"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(98)00061-X"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200946"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/344209"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-9560-5-10"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03470020063033"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/109065799316572"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.4.835"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00739-5"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00739-5"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2272(199911)17:4<298::AID-GEPI5>3.0.CO;2-V"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/89.8.571"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-2416"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.23.2981"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3624"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.735"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.1.7"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905133401901"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/70.4.495"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20505"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(87)90043-6"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1243-2"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38036.646030.EE"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507691788"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1597\/06-151.1"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20507"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3027"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112248"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17445-X"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980630)78:2<155::AID-AJMG11>3.0.CO;2-M"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(03)00086-6"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201603"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510220049033"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0557"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3786"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0475-y"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2009.00529.x"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.11.004"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2004.tb00070.x"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080071"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114509992947"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114509288994"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0779-2"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00297-X"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0290-2"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91743-8"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10029"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.4.962"},{"key":"e_1_2_5_59_1","first-page":"763","article-title":"A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects","volume":"88","author":"Whitehead AS","year":"1995","journal-title":"QJM"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10060"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2879"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1997_034_0206_mcsaoc_2.3.co_2"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199703000-00006"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.20683","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.20683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T15:23:04Z","timestamp":1694618584000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.20683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8]]},"references-count":62,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1002\/bdra.20683"],"URL":"https:\/\/doi.org\/10.1002\/bdra.20683","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8]]}}}