Objective: The purpose of this research was to study factors that are involved in centromeric hypomethylation in the pathogenesis of Down syndrome (DS).
Study design: This was a case-control study to evaluate the association between methyltetrahydrofolate reductase (MTHFR) C677T and methionine synthetase-reductase (MTRR) A66G polymorphisms and the risk of DS; we compared mothers in Italy who had children with DS and matched control subjects.
Results: Seventy-four cases of DS caused by an error in maternal meiosis were compared with 184 matched control subjects. The frequencies of the MTHFR C677T polymorphism were similar between the 2 groups. As regards the MTRR A66G polymorphism, the presence of the mutated G allele either in the heterozygous or homozygous form was significantly more common among mothers of children with DS than among control subjects (odds ratio, 2.21; 95% CI, 1.11-4.40).
Conclusion: In a population with a high prevalence of the mutated T allele, maternal MTRR A66G, but not MTHFR, polymorphisms are associated with Down syndrome.