应用PCR-RFLP方法分析31例唐氏综合征(Down’s syndrome, DS) 患儿母亲和68例正常生育女性叶酸代谢相关基因: MTHFR 677C>T、MTRR 66A>G和MTR 2756A>G多态性, 探讨其与DS发生的关系。采用Pearson χ2 检验基因和基因型频率分布, 并分析各基因之间的相互作用, 计算比值比评价相对危险度。MTHFR基因T等位基因频率在病例组和对照组间具有显著性差异(P<0.05), 而MTRR和MTR基因G等位基因频率差异无显著性。MTHFR TT基因型母亲生育DS患儿风险显著增加(OR=3.51, 95 %CI=1.04-11.85, P<0.05)。MTRR GG基因型母亲生育DS患儿的风险增加3.57倍(OR=3.57, 95 %CI=1.19-10.73, P<0.05)。MTR突变基因型与DS的发生风险无显著关系。MTHFR (CT+TT)/MTRR GG、MTHFR (CT+TT)/MTR AA和MTRR GG/MTR AA联合基因型与DS发生风险显著相关。结果表明, MTHFR 677C>T、MTRR 66A>G位点变异是孕育DS患儿的独立风险因子, 尚不能认为MTR 2756A>G多态与DS发生相关。基因与基因多态位点之间存在交互和修饰效应。

In order to study the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase(MTHFR), methionine synthase reductase(MTRR) and methionine synthase(MTR) involved in folate metabolism and the risk of delivering a child with Down syndrome(DS), polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C>T, MTRR 66A>G, MTR 2756A>G in 31 DS mothers and 68 control mothers. The differences of allelic and genotype frequencies between cases and controls was analyzed by chi-square and OR. Gene-gene interactions were also evaluated. The results showed that significant differences in allelic frequencies were observed between cases and controls for MTHFR(P<0.05), but no significant differences in allelic frequencies were observed for MTRR and MTR. Homozygous MTHFR 677C>T polymorphism was more prevalent among mothers of children with DS than among control mothers, with an odds ratio of 3.51(OR=3.51, 95 %CI=1.04-11.85, P<0.05). In addition, the homozygous MTRR 66A>G polymorphism was independently associated with a 3.57-fold increase in estimated risk (OR=3.57, 95 %CI=1.19-10.73, P<0.05). No significant associations with increased risk of DS were observed for homozygous MTR 2756A>G. Positive interactions were found for following genotype-pairs: MTHFR (CT+TT)/MTRR GG, MTHFR (CT+TT)/MTR AA and MTRR GG/ MTR AA. In conclusion, MTHFR 677C>T and MTRR 66A>G polymorphisms are two independent risk factors for DS. MTR 2756A>G polymorphism is not an independent risk factor. A role for combined genotypes in the risk of DS pregnancies can not be excluded.