{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:11:31Z","timestamp":1761822691310},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T00:00:00Z","timestamp":1092960000000},"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":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) are obstructive malformations of the left ventricular outflow tract that account for a significant proportion of infant mortality. Two previous small case\u2010control studies suggested methylenetetrahydrofolate reductase (MTHFR) polymorphisms may be associated with this group of malformations.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used a family\u2010based association design with inclusion criteria of nonsyndromic diagnosis of AVS, CoA, and HLHS, powered to detect an odds ratio for the heterozygote of &lt;1.5. A total of 207 affected offspring\u2010parent trios were genotyped by restriction fragment length polymorphisms at the two common polymorphic loci C677T and A1298C.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Error rate estimation based on replicate samples was 0.76%. Mendelian inconsistency at either polymorphism was noted in 10 trios, for a calculated undetected error rate of 1.95%. A total of 197 trios were analyzed using the transmission disequilibrium test. Significant association was not found between both the C677T or A1298C polymorphisms and presence of a heart defect, whether analyzed as a group, or by sex, ethnicity, or specific diagnosis. A log\u2010linear analysis did not find increased relative risk based on the maternal genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We were unable to replicate previous association studies and concluded that neither the affected nor the maternal MTHFR genotype, by itself, is a major risk factor for congenital left ventricular outflow tract malformations. Birth Defects Research (Part A), 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20049","type":"journal-article","created":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T20:09:45Z","timestamp":1093032585000},"page":"825-830","source":"Crossref","is-referenced-by-count":30,"title":["A family\u2010based association study of congenital left\u2010sided heart malformations and 5,10 methylenetetrahydrofolate reductase"],"prefix":"10.1002","volume":"70","author":[{"given":"Kim 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