{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T20:15:23Z","timestamp":1770840923677,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> For analyzing the distribution characteristics of MTHFR C677T polymorphism in Chinese females in order to provide information for reducing birth defects and formulating public health policies to prevent congenital malformations.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Literature search in the last 6 years on \u201cMTHFR C677T,\u201d \u201cpolymorphism\u201d and \u201cmethylene tetrahydrofolate reductase.\u201d The included literature provides the MTHFR C677T frequency in healthy females in the corresponding regions. The data were grouped by the national administrative region as a unit to obtain the distribution information of the MTHFR C677T and alleles in the female population in every province, municipality or autonomous region. This was done for analyzing the overall distribution of the MTHFR C677T allele and the geographical distribution of pregnancy complications.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 126 studies were included, covering five autonomous areas, four municipalities directly under the Central Government, as well as 22 provinces (except Taiwan Province) in China. MTHFR C677T polymorphism data of 27 groups of Chinese Han women and 31 groups of other Chinese females were obtained, and the chi-square test revealed notable inter-group differences (<jats:italic>p<\/jats:italic> = 0.000). The TT genotype and T allele of MTHFR C677T accounted for 18.2% (4.7%\u201338.3%) and 40.3% (19.7%\u201361.4%) of the Chinese female population, respectively, with a significant north-south difference. Chinese females had a consistent frequency of the T allele with the geographical distribution of pregnancy complications such as recurrent abortion and preeclampsia.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> With a obvious geographical gradient, the MTHFR C677T polymorphism distribution in Chinese females is consistent with the geographical distribution of multiple pregnancy complications, and the risk assessment for it might be included in primary prevention for birth defects.<\/jats:p>","DOI":"10.3389\/fgene.2023.1139124","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T04:46:03Z","timestamp":1682052363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Regional distribution of the MTHFR C677T polymorphism in Chinese females"],"prefix":"10.3389","volume":"14","author":[{"given":"Hua","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changxi","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rujing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2701548","DOI":"10.1155\/2022\/2701548","article-title":"Intrauterine limb ischemia in patient heterozygous for the 677C>T) RS1801133 (polymorphism of methylenetetrahydrofolate reductase MTHR gene","volume":"2022","author":"Al Hammouri","year":"2022","journal-title":"Case Rep. Pediatr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1179573520962230","DOI":"10.1177\/1179573520962230","article-title":"Hyperhomocysteinemia: Clinical insights","volume":"12","author":"Al Mutairi","year":"2020","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/mnfr.201200108","article-title":"Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C 677 T genotype: Results from a crossover trial","volume":"57","author":"Anderson","year":"2013","journal-title":"Mol. Nutr. food Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1056\/NEJM199911113412001","article-title":"Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative project for neural tube defect prevention","volume":"341","author":"Berry","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1017\/s0007114500000751","article-title":"The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects","volume":"83","author":"Chango","year":"2000","journal-title":"Br. J. Nutr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"710","DOI":"10.11817\/j.issn.1672-7347.2015.07.002","article-title":"Geographical distribution of MTHFR and MTRR gene polymorphisms among the Han women in Zhengzhou city","volume":"40","author":"Cui","year":"2015","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.wasman.2020.11.054","article-title":"Knowledge and intake of folic acid to prevent neural tube defects among pregnant women in urban China: A cross-sectional study","volume":"21","author":"Cui","year":"2021","journal-title":"BMC pregnancy childbirth"},{"key":"B8","doi-asserted-by":"publisher","first-page":"6652231","DOI":"10.1155\/2021\/6652231","article-title":"A novel review of homocysteine and pregnancy complications","volume":"2021","author":"Dai","year":"2021","journal-title":"BioMed Res. Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/jog.13566","article-title":"Systematic review and meta-analysis of the associations between maternal methylenetetrahydrofolate reductase polymorphisms and preterm delivery","volume":"44","author":"Fang","year":"2018","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"B10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0140-6736(91)90133-A","article-title":"Prevention of neural tube defects: Results of the medical research council vitamin study. MRC vitamin study research group","volume":"338","year":"1991","journal-title":"lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3630","DOI":"10.1093\/jn\/133.11.3630","article-title":"Geographical, seasonal and gender differences in folate status among Chinese adults","volume":"133","author":"Hao","year":"2003","journal-title":"J. Nutr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.2485\/jhtb.30.297","article-title":"Association of <i>MTHFR<\/i> C677T, <i>MTHFR<\/i> A1298C and <i>MTRR<\/i> A66G Polymorphisms with Birth Defects in Southern China","volume":"30","author":"Jiang","year":"2021","journal-title":"J. Hard Tissue Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1111\/jog.14770","article-title":"The impact of micronutrient deficiency on pregnancy complications and development origin of health and disease","volume":"47","author":"Kanasaki","year":"2021","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jmbbm.2017.06.028","article-title":"Impact of periconceptional folic acid supplementation on low birth weight and small-for-gestational-age infants in China: A large prospective cohort study","volume":"187","author":"Li","year":"2017","journal-title":"J. Pediatr."},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.2139\/ssrn.3974539","article-title":"Folic acid supplements and perinatal mortality in China","author":"Li","year":"2021"},{"key":"B16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1159\/000367656","article-title":"Individualized supplementation of folic acid according to polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) reduced pregnant complications","volume":"79","author":"Li","year":"2015","journal-title":"Gynecol. obstetric investigation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1111\/jch.14248","article-title":"Morbidity and maternal and infant outcomes of hypertensive disorder in pregnancy in China in 2018","volume":"23","author":"Lyu","year":"2021","journal-title":"J. Clin. Hypertens."},{"key":"B18","doi-asserted-by":"publisher","first-page":"113","DOI":"10.4103\/aam.aam_41_19","article-title":"Association between maternal serum homocysteine concentrations in early pregnancy and adverse pregnancy outcomes","volume":"19","author":"Nwogu","year":"2020","journal-title":"Ann. Afr. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1093\/humrep\/deaa095","article-title":"Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses","volume":"35","author":"Ota","year":"2020","journal-title":"Hum. Reprod."},{"key":"B20","doi-asserted-by":"publisher","first-page":"463","DOI":"10.22074\/ijfs.2015.4186","article-title":"Association between maternal MTHFR polymorphisms and nonsyndromic cleft lip with or without cleft palate in offspring, a meta-analysis based on 15 case-control studies","volume":"8","author":"Pan","year":"2015","journal-title":"Int. J. Fertil. Steril."},{"key":"B21","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.procbio.2023.01.017","article-title":"The role of prognostic biomarkers and their implications in early detection of preeclampsia: A systematic review","volume":"126","author":"Parthasarathy","year":"2023","journal-title":"Process Biochem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1086\/302015","article-title":"Heterogeneity in world distribution of the thermolabile C677T mutation in 5, 10-methylenetetrahydrofolate reductase","volume":"63","author":"Pepe","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e108552","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":"B24","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1017\/S1368980007246786","article-title":"Comparison of blood folate levels among pregnant Chinese women in areas with high and low prevalence of neural tube defects","volume":"10","author":"Ren","year":"2007","journal-title":"Public health Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.3760\/cma.j.issn.0254-6450.2019.09.020","article-title":"Risk factors for preterm birth, low birth weight and small for gestational age: A prospective cohort study","volume":"40","author":"Shen","year":"2019","journal-title":"Zhonghua liu xing bing xue za zhi= Zhonghua liuxingbingxue zazhi"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1753-4887.1996.tb03770.x","article-title":"Biological chemistry of thiols in the vasculature and in vascular-related disease","volume":"54","author":"Stamler","year":"1996","journal-title":"Nutr. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/15513815.2020.1775734","article-title":"Association of fetal MTHFR C677T polymorphism with susceptibility to neural tube defects: A systematic review and update meta-analysis","volume":"41","author":"Tabatabaei","year":"2022","journal-title":"Fetal Pediatr. pathology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fnut.2019.00049","article-title":"Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies","volume":"6","author":"Tinelli","year":"2019","journal-title":"Front. Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1177\/153537020122600402","article-title":"Folate, homocysteine and neural tube defects: An overview","volume":"226","author":"Van Der Put","year":"2001","journal-title":"Exp. Biol. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1186\/1471-2458-11-925","article-title":"Dietary patterns and hypertension among Chinese adults: A nationally representative cross-sectional study","volume":"11","author":"Wang","year":"2011","journal-title":"BMC public health"},{"key":"B31","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1136\/jmg.40.8.619","article-title":"Geographical and ethnic variation of the 677C> T allele of 5, 10 methylenetetrahydrofolate reductase (MTHFR): Findings from over 7000 newborns from 16 areas world wide","volume":"40","author":"Wilcken","year":"2003","journal-title":"J. Med. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e57917","DOI":"10.1371\/journal.pone.0057917","article-title":"Geographical distribution of MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in China: Findings from 15357 adults of han nationality","volume":"8","author":"Yang","year":"2013","journal-title":"PloS one"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1111\/jog.13989","article-title":"Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage","volume":"45","author":"Zarfeshan Fard","year":"2019","journal-title":"J. Obstetrics Gynaecol. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1159\/000488267","article-title":"Two common MTHFR gene polymorphisms (C677T and A1298C) and fetal congenital heart disease risk: An updated meta-analysis with trial sequential analysis","volume":"45","author":"Zhang","year":"2018","journal-title":"Cell. Physiology Biochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/1471-0528.16458","article-title":"Stillbirths in China: A nationwide survey","volume":"128","author":"Zhu","year":"2021","journal-title":"Bjog"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e219382","DOI":"10.1001\/jamanetworkopen.2021.9382","article-title":"Mortality and morbidity of infants born extremely preterm at tertiary medical centers in China from 2010 to 2019","volume":"4","author":"Zhu","year":"2021","journal-title":"JAMA Netw. open"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1139124\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T08:31:45Z","timestamp":1683880305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1139124\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":36,"alternative-id":["10.3389\/fgene.2023.1139124"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1139124","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]},"article-number":"1139124"}}