{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:30:03Z","timestamp":1789846203529,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T00:00:00Z","timestamp":1282003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiac abnormalities are one of the most common congenital defects observed in individuals with Down syndrome. Considerable research has implicated both folate deficiency and genetic variation in folate pathway genes with birth defects, including both congenital heart defects (CHD) and Down syndrome (DS). Here, we test variation in folate pathway genes for a role in the major DS\u2010associated CHD atrioventricular septal defect (AVSD). In a group of 121 case families (mother, father, and proband with DS and AVSD) and 122 control families (mother, father, and proband with DS and no CHD), tag SNPs were genotyped in and around five folate pathway genes: 5,10\u2010methylenetetrahyrdofolate reductase (<jats:italic>MTHFR<\/jats:italic>), methionine synthase (<jats:italic>MTR<\/jats:italic>), methionine synthase reductase (<jats:italic>MTRR<\/jats:italic>), cystathionine \u03b2\u2010synthase (<jats:italic>CBS<\/jats:italic>), and the reduced folate carrier (<jats:italic>SLC19A1<\/jats:italic>, <jats:italic>RFC1<\/jats:italic>). <jats:italic>SLC19A1<\/jats:italic> was found to be associated with AVSD using a multilocus allele\u2010sharing test. Individual SNP tests also showed nominally significant associations with odds ratios of between 1.34 and 3.78, depending on the SNP and genetic model. Interestingly, all marginally significant SNPs in <jats:italic>SLC19A1<\/jats:italic> are in strong linkage disequilibrium (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u22650.8) with the nonsynonymous coding SNP rs1051266 (c.80A&gt;G), which has previously been associated with nonsyndromic cases of CHD. In addition to <jats:italic>SLC19A1<\/jats:italic>, the known functional polymorphism <jats:italic>MTHFR<\/jats:italic> c.1298A was over\u2010transmitted to cases with AVSD (<jats:italic>P<\/jats:italic>=0.05) and under\u2010transmitted to controls (<jats:italic>P<\/jats:italic>=0.02). We conclude, therefore, that disruption of the folate pathway contributes to the incidence of AVSD among individuals with DS. <jats:italic>Genet. Epidemiol<\/jats:italic>. 34: 603\u2013612, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gepi.20518","type":"journal-article","created":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T23:56:27Z","timestamp":1282089387000},"page":"613-623","source":"Crossref","is-referenced-by-count":67,"title":["Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome"],"prefix":"10.1002","volume":"34","author":[{"given":"Adam E.","family":"Locke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Dooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart W.","family":"Tinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo 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