OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use. RESULTS: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls. CONCLUSION: Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome.
OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use. RESULTS: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls. CONCLUSION:Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome.
Authors: Helena C Parkington; Kelly R Kenna; Foula Sozo; Harold A Coleman; Alan Bocking; James F Brien; Richard Harding; David W Walker; Ruth Morley; Marianne Tare Journal: J Physiol Date: 2014-04-22 Impact factor: 5.182
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: Shimul Chowdhury; Mario A Cleves; Stewart L MacLeod; S Jill James; Weizhi Zhao; Charlotte A Hobbs Journal: Birth Defects Res A Clin Mol Teratol Date: 2011-01-19
Authors: Shimul Chowdhury; Stephen W Erickson; Stewart L MacLeod; Mario A Cleves; Ping Hu; Mohammad A Karim; Charlotte A Hobbs Journal: PLoS One Date: 2011-01-24 Impact factor: 3.240
Authors: Régine P Steegers-Theunissen; Sylvia A Obermann-Borst; Dennis Kremer; Jan Lindemans; Cissy Siebel; Eric A Steegers; P Eline Slagboom; Bastiaan T Heijmans Journal: PLoS One Date: 2009-11-16 Impact factor: 3.240