年轻母亲叶酸代谢基因多态性与唐氏综合征发生的关系
收稿日期: 2009-09-28
修回日期: 2010-03-06
网络出版日期: 2010-05-05
基金资助
安徽省高等学校省级自然科学研究项目(编号: KJ2009B084Z)和蚌埠医学院自然科学研究项目(编号: BY0709)资助
Folate gene polymorphism and the risk of Down syndrome pregnan-cies in young Chinese women
Received date: 2009-09-28
Revised date: 2010-03-06
Online published: 2010-05-05
为探讨年轻母亲叶酸代谢相关基因MTHFR 677C>T、MTRR 66A>G、RFC-1 80G>A和MTR 2756A>G多态性与唐氏综合征(Down syndrome, DS)发生的关系, 采用随机病例-对照研究设计, 应用PCR-RFLP方法检测60例DS患儿的母亲与68例正常生育女性的基因型。经χ2 检验, MTHFR基因T等位基因频率在病例组和对照组中差异有统计学意义(P<0.05), 而MTRR、MTR和 RFC-1等位基因频率差异无统计学意义。Logistic回归分析显示: 携带MTHFR TT基因型的母亲孕育DS患儿的风险显著增加(OR=3.51, 95% CI=1.30~9.46, P<0.05), 而杂合子CT以及CT合并TT基因型与DS发生风险无显著关联; 携带MTRR GG基因型的母亲孕育DS患儿的风险增加3.16倍(OR=3.16, 95% CI=1.20~8.35, P<0.05), 而RFC-1和MTR突变基因型与DS发生风险无显著关联; MTHFR(CT+TT)/MTRR GG、MTHFR (CT+TT)/ RFC-1 AA、MTHFR CC / MTR (AG +GG)、 MTHFR (CT+TT)/MTR AA、MTRR GG/MTR AA和RFC-1 AA / MTR AA联合基因型与DS发生风险显著相关。结果表明, 年轻女性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RFC-1 80G>A、MTR 2756A>G多态性与DS发生相关, 而基因与基因多态位点之间存在交互和修饰效应。
廖亚平，鲍明升，刘长青，刘辉，张鼎 . 年轻母亲叶酸代谢基因多态性与唐氏综合征发生的关系[J]. 遗传, 2010 , 32(5) : 461 -466 . DOI: 10.3724/SP.J.1005.2010.00461
To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), reduced folate carrier1 (RFC-1), methionine synthase (MTR) involved in folate metabolism and the risk of offsprings of young Chinese women with Down syndrome (DS) through a case-control study, the polymorphisms of MTHFR 677C>T, MTRR 66A>G, RFC-1 80G>A, and MTR 2756A>G in 60 mothers of children with DS and 68 control mothers were investigated by PCR-RFLP. Significant differences in alle-lic frequencies were present between the cases and controls for MTHFR (P<0.05), but not in allelic frequencies for MTRR, RFC-1, and MTR. Homozygous MTHFR 677C>T polymorphism was more prevalent among the mothers of children with DS than among the control mothers, with an odds ratio of 3.51 (OR=3.51, 95% CI=1.30~9.46, P<0.05). No significant association was observed in the combined heterozygotes. In addition, the homozygous MTRR 66A>G polymorphism was independently associated with a 3.16-fold increase in estimated risk (OR=3.16, 95% CI=1.20~8.35, P<0.05). The increased risk of DS for homozygous RFC-1 80G>A was not associated with MTR 2756A>G. Positive interactions were found for the following genotype-pairs: MTHFR(CT+TT)/MTRR GG, MTHFR (CT+TT)/RFC-1 AA, MTHFR CC/MTR(AG+GG), MTHFR (CT+TT)/MTR AA, MTRR GG/MTR AA, and RFC-1 AA/MTRAA. In conclusion, MTHFR 677C>T and MTRR 66A>G polymorphisms are two independent risk factors for DS pregnancies in young women, but RFC-1 80G>A and MTR 2756A>G polymorphism are not independent risk factor. A role for combined genotypes in the risk of DS pregnancies cannot be excluded.
Key words： Down syndrome; MTHFR; MTRR; RFC-1; MTR; polymorphism
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