BACKGROUND: 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-control studies suggested methylenetetrahydrofolate reductase (MTHFR) polymorphisms may be associated with this group of malformations. METHODS: We used a family-based association design with inclusion criteria of nonsyndromic diagnosis of AVS, CoA, and HLHS, powered to detect an odds ratio for the heterozygote of <1.5. A total of 207 affected offspring-parent trios were genotyped by restriction fragment length polymorphisms at the two common polymorphic loci C677T and A1298C. RESULTS: 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-linear analysis did not find increased relative risk based on the maternal genotype. CONCLUSIONS: 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. (c) 2004 Wiley-Liss, Inc.
BACKGROUND: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-control studies suggested methylenetetrahydrofolate reductase (MTHFR) polymorphisms may be associated with this group of malformations. METHODS: We used a family-based association design with inclusion criteria of nonsyndromic diagnosis of AVS, CoA, and HLHS, powered to detect an odds ratio for the heterozygote of <1.5. A total of 207 affected offspring-parent trios were genotyped by restriction fragment length polymorphisms at the two common polymorphic loci C677T and A1298C. RESULTS: 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-linear analysis did not find increased relative risk based on the maternal genotype. CONCLUSIONS: 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. (c) 2004 Wiley-Liss, Inc.
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Authors: Kim L McBride; Lisa Marengo; Mark Canfield; Peter Langlois; David Fixler; John W Belmont Journal: Birth Defects Res A Clin Mol Teratol Date: 2005-08
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Authors: Laura E Mitchell; Jin Long; Jennifer Garbarini; Prasuna Paluru; Elizabeth Goldmuntz Journal: Birth Defects Res A Clin Mol Teratol Date: 2010-01
Authors: Neil A Hanchard; Shanker Swaminathan; Kristine Bucasas; Dieter Furthner; Susan Fernbach; Mahshid S Azamian; Xueqing Wang; Mark Lewin; Jeffrey A Towbin; Lisa C A D'Alessandro; Shaine A Morris; William Dreyer; Susan Denfield; Nancy A Ayres; Wayne J Franklin; Henri Justino; M Regina Lantin-Hermoso; Elena C Ocampo; Alexia B Santos; Dhaval Parekh; Douglas Moodie; Aamir Jeewa; Emily Lawrence; Hugh D Allen; Daniel J Penny; Charles D Fraser; James R Lupski; Mojisola Popoola; Lalita Wadhwa; J David Brook; Frances A Bu'Lock; Shoumo Bhattacharya; Seema R Lalani; Gloria A Zender; Sara M Fitzgerald-Butt; Jessica Bowman; Don Corsmeier; Peter White; Kelsey Lecerf; Gladys Zapata; Patricia Hernandez; Judith A Goodship; Vidu Garg; Bernard D Keavney; Suzanne M Leal; Heather J Cordell; John W Belmont; Kim L McBride Journal: Hum Mol Genet Date: 2016-03-09 Impact factor: 6.150