OBJECTIVETo investigate whether the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism is associated with Down syndrome (DS).

METHODSOne hundred Chinese mothers who gave birth to babies with DS and 100 control mothers were chosen. Genotype of MTHFR 677 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and concentration of plasma homocysteine (HCY) was measured by chemiluminescence.

RESULTSThe MTHFR 677T allele frequency was significantly different among case mothers, compared with control mothers (P=0.002); the odds ratio for the heterozygous CT genotype was 2.12 (95%CI: 1.14-3.94), whereas for the homozygous TT genotype, the odds ratio was 3.43 (95%CI:1.41-8.36). The mean plasma HCY concentration [(9.04 +/- 3.85) mu mol/L] of cases was significantly different from that of controls [(6.53 +/- 2.06) mu mol/L](P <0.01). The presence of the 677C>T substitution in one or both alleles was associated with increased plasma HCY both in case mothers and control mothers (P < 0.01). Interestingly, although both being MTHFR 677CC, the plasma HCY concentrations were higher in case mothers than in control mothers, the increase was not dependent on MTHFR genotype (P < 0.01).

CONCLUSIONOur results provide evidences that plasma HCY and genetic polymorphism in gene of folate pathway are risk factors for mothers to have a DS child in China.