ArticleGenetic epidemiology2010
Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome.
Article in Genetic epidemiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 8 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 8 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies.Italian journal of pediatrics · 2017Pooled it
- Gender differences in the prevalence of congenital heart disease in Down's syndrome: a brief meta-analysis.BMC medical genetics · 2017Pooled it
- Pooled it
- Association between methionine synthase reductase A66G polymorphism and the risk of congenital heart defects: evidence from eight case-control studies.Pediatric cardiology · 2014Pooled it
- Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis.PloS one · 2014Pooled it
- The MTR 2756A>G polymorphism and maternal risk of birth of a child with Down syndrome: a case-control study and a meta-analysis.Molecular biology reports · 2013Pooled it
- The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis.Nutrients · 2013Pooled it
- [Turner syndrome and genetic polymorphism: a systematic review].Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao PauloPooled it
- Complete chromosome 21 centromere sequencing of families with Down syndrome.American journal of human genetics · 2026Article
- A multicenter observational cohort study in survivors of Down Syndrome-associated acute leukemia (ALTE22C1): a report from the Children's Oncology Group.BMC cancer · 2025Observational
- Complete chromosome 21 centromere sequencing of families with Down syndrome reveals centromere size asymmetry.bioRxiv : the preprint server for biology · 2025Article
- Review
- Human Genetics of Atrioventricular Septal Defect.Advances in experimental medicine and biology · 2024Review
- Article
- Review
- Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti-tuberculosis drug-induced hepatotoxicity: A prospective study.Journal of clinical laboratory analysis · 2021Article
- Congenital heart defects among Down's syndrome cases: an updated review from basic research to an emerging diagnostics technology and genetic counselling.Journal of genetics · 2021Review
- Molecular mechanisms of congenital heart disease in down syndrome.Genes & diseases · 2019Review
- Mature miR-99a Upregulation in the Amniotic Fluid Samples from Female Fetus Down Syndrome Pregnancies: A Pilot Study.Medicina (Kaunas, Lithuania) · 2019Article
- Survey of Human Chromosome 21 Gene Expression Effects on Early Development inG3 (Bethesda, Md.) · 2018Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
Cardiac abnormalities are one of the most common congenital defects observed in individuals with Down syndrome. Considerable research has implicated both folate deficiency and genetic variation in folate pathway genes with birth defects, including both congenital heart defects (CHD) and Down syndrome (DS). Here, we test variation in folate pathway genes for a role in the major DS-associated CHD atrioventricular septal defect (AVSD). In a group of 121 case families (mother, father, and proband with DS and AVSD) and 122 control families (mother, father, and proband with DS and no CHD), tag SNPs were genotyped in and around five folate pathway genes: 5,10-methylenetetrahyrdofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), cystathionine beta-synthase (CBS), and the reduced folate carrier (SLC19A1, RFC1). SLC19A1 was found to be associated with AVSD using a multilocus allele-sharing test. Individual SNP tests also showed nominally significant associations with odds ratios of between 1.34 and 3.78, depending on the SNP and genetic model. Interestingly, all marginally significant SNPs in SLC19A1 are in strong linkage disequilibrium (r(2)> or = 0.8) with the nonsynonymous coding SNP rs1051266 (c.80A>G), which has previously been associated with nonsyndromic cases of CHD. In addition to SLC19A1, the known functional polymorphism MTHFR c.1298A was over-transmitted to cases with AVSD (P=0.05) and under-transmitted to controls (P=0.02). We conclude, therefore, that disruption of the folate pathway contributes to the incidence of AVSD among individuals with DS.
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Registered trials
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