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Abstract: Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78~8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90~14.22). The combined presence of both polymorphisms was associated with a greater risk of down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058~17.496). The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to down syndrome, and CT, TT and GG gene mutation types increase the risk of down syndrome.

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