Molecular genetics and metabolism, 2012-11, Vol.107 (3), p.596-604
2012
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- Autor(en) / Beteiligte
- Titel
- Associations between maternal genotypes and metabolites implicated in congenital heart defects
- Ist Teil von
- Molecular genetics and metabolism, 2012-11, Vol.107 (3), p.596-604
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The development of non-syndromic congenital heart defects (CHDs) involves a complex interplay of genetics, metabolism, and lifestyle. Previous studies have implicated maternal single nucleotide polymorphisms (SNPs) and altered metabolism in folate-related pathways as CHD risk factors. We sought to discover associations between maternal SNPs and metabolites involved in the homocysteine, folate, and transsulfuration pathways, and determine if these associations differ between CHD cases and controls. Genetic, metabolic, demographic, and lifestyle information was available for 335 mothers with CHD-affected pregnancies and 263 mothers with unaffected pregnancies. Analysis was conducted on 1160 SNPs, 13 plasma metabolites, and 2 metabolite ratios. A two-stage multiple linear regression was fitted to each combination of SNP and metabolite/ratio. We identified 4 SNPs in the methionine adenosyltransferase II alpha (MAT2A) gene that were associated with methionine levels. Three SNPs in tRNA aspartic acid methyltransferase 1 (TRDMT1) gene were associated with total plasma folate levels. Glutamylcysteine (GluCys) levels were associated with multiple SNPs within the glutathione peroxidase 6 (GPX6) and O-6-methylguanine-DNA methyltransferase (MGMT) genes. The regression model revealed interactions between genotype and case–control status in the association of total plasma folate, total glutathione (GSH), and free GSH, to SNPs within the MGMT, 5,10-methenyltetrahydrofolate synthetase (MTHFS), and catalase (CAT) genes, respectively. Our study provides further evidence that genetic variation within folate-related pathways accounts for inter-individual variability in key metabolites. We identified specific SNP–metabolite relationships that differed in mothers with CHD-affected pregnancies, compared to controls. Our results underscore the importance of multifactorial studies to define maternal CHD risk. ► We investigate maternal genetic variation and metabolism in congenital heart defects. ► Maternal SNPs and metabolites involved in folate metabolism were analyzed. ► Multiple associations were found between maternal SNPs and metabolites. ► Interactions between SNPs and metabolites were dependent on case–control status. ► Results underscore the importance of multifactorial studies to define CHD risk.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1096-7192eISSN: 1096-7206DOI: 10.1016/j.ymgme.2012.09.022Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3523122
- Format
- –
- Schlagworte
- Adult, Asymptomatic Diseases, Carbon-Nitrogen Ligases - genetics, Carbon-Nitrogen Ligases - metabolism, Case-Control Studies, Catalase - genetics, Catalase - metabolism, Congenital heart defects (CHDs), DNA (Cytosine-5-)-Methyltransferases - genetics, DNA (Cytosine-5-)-Methyltransferases - metabolism, DNA Modification Methylases - genetics, DNA Modification Methylases - metabolism, DNA Repair Enzymes - genetics, DNA Repair Enzymes - metabolism, Female, Folate pathway, Folic Acid - metabolism, Genotype, Glutathione - metabolism, Glutathione Peroxidase - genetics, Glutathione Peroxidase - metabolism, Heart Defects, Congenital - genetics, Heart Defects, Congenital - metabolism, Heart Defects, Congenital - pathology, Homocysteine - metabolism, Humans, Life Style, Male, Maternal genotypes, Metabolites, Methionine - metabolism, Methionine Adenosyltransferase - genetics, Methionine Adenosyltransferase - metabolism, Polymorphism, Single Nucleotide, Risk, Single nucleotide polymorphisms (SNPs), Tumor Suppressor Proteins - genetics, Tumor Suppressor Proteins - metabolism