{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:58:35Z","timestamp":1790974715156,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,5,7]],"date-time":"2007-05-07T00:00:00Z","timestamp":1178496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periconceptional maternal folic acid supplementation can prevent up to 70% of pregnancies affected with neural tube defects (NTDs), including spina bifida. This has focused attention on folate\u2010related genes such as dihydrofolate reductase (<jats:italic>DHFR<\/jats:italic>) in a bid to identify the genetic factors that influence NTD risk through either the fetal or maternal genotype. We considered a novel intronic 19\u2010bp deletion polymorphism and two polymorphisms within the 3\u2032 untranslated region (721A\u2009&gt;\u2009T and 829C\u2009&gt;\u2009T) of the <jats:italic>DHFR<\/jats:italic> gene as candidates for NTD risk. We studied NTD cases (n\u2009=\u2009283), mothers of cases (n\u2009=\u2009280), fathers of cases (n\u2009=\u2009279), and controls (n\u2009=\u2009256). We did not find the DHFR 829C\u2009&gt;\u2009T polymorphism to be variable within the Irish population. The 19\u2010bp intron deletion and the 721A\u2009&gt;\u2009T polymorphisms were found to be in linkage disequilibrium. In contrast to a previous study, the 19\u2010bp intron deletion allele did show a significant protective effect in mothers of NTD cases when present in one (relative risk 0.59 [95%CI: 0.39\u20130.89], <jats:italic>P<\/jats:italic>\u2009=\u20090.01) or two copies (relative risk 0.52 [95%CI: 0.32\u20130.86], <jats:italic>P<\/jats:italic>\u2009=\u20090.01). Analysis of mRNA levels revealed a small increase in expression (\u223c1.5\u2010fold) associated with the 19\u2010bp intron deletion polymorphism, but this was not significant. In conclusion, the <jats:italic>DHFR<\/jats:italic> intron 19\u2010bp deletion allele may be a protective NTD genetic factor by increasing <jats:italic>DHFR<\/jats:italic> mRNA levels in pregnant women. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31725","type":"journal-article","created":{"date-parts":[[2007,5,7]],"date-time":"2007-05-07T20:48:01Z","timestamp":1178570881000},"page":"1174-1180","source":"Crossref","is-referenced-by-count":52,"title":["The 19\u2010bp deletion polymorphism in intron\u20101 of dihydrofolate reductase (<i>DHFR<\/i>) may decrease rather than increase risk for spina bifida in the Irish population"],"prefix":"10.1002","volume":"143A","author":[{"given":"Anne","family":"Parle\u2010McDermott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Pangilinan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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