MTHFR、MTRR和MTR基因多态性与唐氏综合征发生的相关性研究

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，探讨其与唐氏综合征DS发生的关系。采用Pearson χ^2 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中具有显著性差异（P〈0.05），而MTRR和MTR基因G等位基因频率在病例组和对照组中的差异无显著性。MTHFR TT基因型母亲生育DS风险显著增加（OR=3.51，95 %CI=1.04-11.85，P〈0.05）。MTRR GG基因型生育DS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AG和GG与生育DS的风险无显著关系。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位点变异是生育DS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。

Relationship between the Polymorphisms in Genes of MTHFR, MTRR and MTR and the Risk of Delivering a Child with Down's Syndrome

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 show 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 is 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.