遗传 ›› 2010, Vol. 32 ›› Issue (5): 461-466.doi: 10.3724/SP.J.1005.2010.00461

• 研究报告 • 上一篇    下一篇

年轻母亲叶酸代谢基因多态性与唐氏综合征发生的关系

廖亚平, 鲍明升, 刘长青, 刘辉, 张鼎   

  1. 蚌埠医学院细胞生物学教研室, 蚌埠 233030
  • 收稿日期:2009-09-28 修回日期:2010-03-06 出版日期:2010-05-20 发布日期: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

LIAO Ya-Ping, BAO Ming-Sheng, LIU Chang-Qing, LIU Hui, ZHANG Ding   

  1. Department of Cell Biology, Bengbu Medical College, Bengbu 233030, China
  • Received:2009-09-28 Revised:2010-03-06 Online:2010-05-20 Published:2010-05-05

摘要:

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MTRRMTRRFC-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-1MTR突变基因型与DS发生风险无显著关联; MTHFR(CT+TT)/MTRR GGMTHFR (CT+TT)/ RFC-1 AAMTHFR CC / MTR (AG +GG)、 MTHFR (CT+TT)/MTR AAMTRR GG/MTR AARFC-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。

关键词: 唐氏综合征, 亚甲基四氢叶酸还原酶, 甲硫氨酸合成还原酶, 还原叶酸载体基因, 蛋氨酸合酶, 多态性

Abstract:

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