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In 2009, I reviewed the literature in the field, concluding that at that time no single gene could be clearly linked to the maternal risk of birth of a child with DS, due to the relatively small sample-size and the conflicting nature of the findings among the different studies (Copped, 1), and literature meta-analyses are nowadays available overall suggesting that at least three polymorphisms of folate pathway genes are likely to be associated to the maternal risk for trisomy 21 (Table 2), while an increasing number of studies also suggest complex gene-gene and gene-nutrient interactions (Tables 1, 3)

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