BACKGROUND: Although congenital heart defects (CHD) are the most common and serious group of birth defects, relatively little is known about the causes of these conditions and there are no established prevention strategies. There is evidence suggesting that the risk of CHD in general, and conotruncal and ventricular septal defects in particular, may be related to maternal folate status as well as genetic variants in folate-related genes. However, efforts to establish the relationships between these factors and CHD risk have been hampered by a number of factors including small study sample sizes and phenotypic heterogeneity. METHODS AND RESULTS: The present study examined the relationships between variation in 9 folate-related genes and a subset of CHD phenotypes (ie, conotruncal defects, perimembranous and malalignment type ventricular septal defects, and isolated aortic arch anomalies) in a cohort of >700 case-parent triads. Further, both maternal and embryonic genetic effects were considered. Analyses of the study data confirmed an earlier reported association between embryonic genotype for MTHFR A1298C and disease risk (unadjusted P=0.002). CONCLUSIONS: These results represent the most comprehensive and powerful analysis of the relationship between CHD and folate-related genes reported to date, and provide additional evidence that, similar to neural tube defects, this subset of CHD is folate related.
BACKGROUND: Although congenital heart defects (CHD) are the most common and serious group of birth defects, relatively little is known about the causes of these conditions and there are no established prevention strategies. There is evidence suggesting that the risk of CHD in general, and conotruncal and ventricular septal defects in particular, may be related to maternal folate status as well as genetic variants in folate-related genes. However, efforts to establish the relationships between these factors and CHD risk have been hampered by a number of factors including small study sample sizes and phenotypic heterogeneity. METHODS AND RESULTS: The present study examined the relationships between variation in 9 folate-related genes and a subset of CHD phenotypes (ie, conotruncal defects, perimembranous and malalignment type ventricular septal defects, and isolated aortic arch anomalies) in a cohort of >700 case-parent triads. Further, both maternal and embryonic genetic effects were considered. Analyses of the study data confirmed an earlier reported association between embryonic genotype for MTHFRA1298C and disease risk (unadjusted P=0.002). CONCLUSIONS: These results represent the most comprehensive and powerful analysis of the relationship between CHD and folate-related genes reported to date, and provide additional evidence that, similar to neural tube defects, this subset of CHD is folate related.
Authors: Yong Li; Jun Cheng; Wen-li Zhu; Jing-jing Dao; Li-ying Yan; Meng-yi Li; Shu-qin Li Journal: Beijing Da Xue Xue Bao Yi Xue Ban Date: 2005-02-18
Authors: Mark A Canfield; Julianne S Collins; Lorenzo D Botto; Laura J Williams; Cara T Mai; Russell S Kirby; Kay Pearson; Owen Devine; Joe Mulinare Journal: Birth Defects Res A Clin Mol Teratol Date: 2005-10
Authors: Mary Ella Pierpont; Craig T Basson; D Woodrow Benson; Bruce D Gelb; Therese M Giglia; Elizabeth Goldmuntz; Glenn McGee; Craig A Sable; Deepak Srivastava; Catherine L Webb Journal: Circulation Date: 2007-05-22 Impact factor: 29.690
Authors: Lora J H Bean; Emily G Allen; Stuart W Tinker; Natasha D Hollis; Adam E Locke; Charlotte Druschel; Charlotte A Hobbs; Leslie O'Leary; Paul A Romitti; Marjorie H Royle; Claudine P Torfs; Kenneth J Dooley; Sallie B Freeman; Stephanie L Sherman Journal: Birth Defects Res A Clin Mol Teratol Date: 2011-08-24
Authors: Shimul Chowdhury; Charlotte A Hobbs; Stewart L MacLeod; Mario A Cleves; Stepan Melnyk; S Jill James; Ping Hu; Stephen W Erickson Journal: Mol Genet Metab Date: 2012-09-27 Impact factor: 4.797
Authors: Ming Li; Stephen W Erickson; Charlotte A Hobbs; Jingyun Li; Xinyu Tang; Todd G Nick; Stewart L Macleod; Mario A Cleves Journal: Genet Epidemiol Date: 2014-03-02 Impact factor: 2.135
Authors: Laura E Mitchell; Jin Long; Jennifer Garbarini; Prasuna Paluru; Elizabeth Goldmuntz Journal: Birth Defects Res A Clin Mol Teratol Date: 2010-01
Authors: Ming Li; Jingyun Li; Changshuai Wei; Qing Lu; Xinyu Tang; Stephen W Erickson; Stewart L MacLeod; Charlotte A Hobbs Journal: Ann Hum Genet Date: 2015-11-27 Impact factor: 1.670
Authors: Ming Li; Mario A Cleves; Himel Mallick; Stephen W Erickson; Xinyu Tang; Todd G Nick; Stewart L Macleod; Charlotte A Hobbs Journal: Hum Genet Date: 2014-06-04 Impact factor: 4.132