MTRR and MTHFR polymorphism: Link to Down syndrome?
MTRR and MTHFR polymorphism: Link to Down syndrome?
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DOI：
10.1002/ajmg.10121
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发表时间：
2002-01-15
期刊：
影响因子：
--
通讯作者：
Mills, JL
中科院分区：
文献类型：
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作者：
O'Leary, VB;Parle-McDermott, A;Mills, JL
叶酸代谢酶亚甲基四氢叶酸还原酶(MTHFR C677T)和蛋氨酸合成酶还原酶(MTRR A66G)基因的多态性与唐氏综合征的病因有关。我们检测了生下唐氏综合征孩子的母亲(n=48)和对照组母亲(n=192)中这些变异基因的患病率，并调查了MTRA66G和MTHFR C677T的存在对生化因素的影响。唐氏综合征患儿母亲MTR型(AG、GG)频率显著高于对照组(P=0.0028)。唐氏综合征患儿母亲MTHFR C677T基因频率无明显变化(P=0.74)。然而，具有MTHFR CT或TT基因和MTRGG基因的母亲生下唐氏综合症的风险增加了2.98倍(P=0.02)。MTRR基因多态性不会增加血浆同型半胱氨酸水平。MTHFR T等位基因携带者同型半胱氨酸水平较高。总而言之，MTRA66G在唐氏综合症儿童的母亲中更为常见，但似乎并不会通过改变同型半胱氨酸代谢来增加患唐氏综合症的风险。同时拥有MTRR和MTHFR变异基因的女性生下唐氏综合症后代的风险也会增加。(C)2001年Wiley-Liss，Inc.
Polymorphisms in genes encoding the folate metabolizing enzymes methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase reductase (MTRR A66G) have been linked to the etiology of Down syndrome. We examined the prevalence of these variant genotypes in mothers who had given birth to a child with Down syndrome (n = 48) and in control mothers (n = 192), and investigated the biochemical factors influenced by the presence of MTRR A66G and MTHFR C677T. The frequency of the MTRR variant genotypes (AG, GG) was significantly higher in mothers of children with Down syndrome compared to controls (P = 0.0028). MTHFR C677T genotype frequencies were not significantly altered in mothers of children with Down syndrome (P = 0.74). However, mothers who had a MTHFR CT or TT genotype and a MTRR GG genotype had a 2.98-fold increased risk of having a child with Down syndrome (P = 0.02). The MTRR polymorphism did not increase plasma homocysteine. Higher homocysteine was found with the presence of the MTHFR T allele. In conclusion, MTRR A66G is significantly more common in mothers of children with Down syndrome but does not appear to increase the risk for Down syndrome by changing homocysteine metabolism. Women who have both the MTRR and MTHFR variant genotypes are also at increased risk of producing offspring with Down syndrome. (C) 2001 Wiley-Liss, Inc.