Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy
Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy
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DOI：
10.1016/j.ymgme.2003.12.010
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发表时间：
2004-04-01
影响因子：
3.8
通讯作者：
Burn, J
中科院分区：
文献类型：
--
作者：
Relton, CL;Wilding, CS;Burn, J
先前的研究表明，叶酸相关基因的多态性变异与神经管缺陷妊娠的风险之间存在矛盾。最近的证据表明，母亲基因型是决定NTD风险的重要因素。对来自英国北部地区的97名NTD病例的母亲进行了病例对照研究。从区域DNA银行招募孕妇对照组（n = 190）和来自同一地理区域的非孕妇对照组（n = 100）。测定MTHFR 677C>T、MTHFR 1298A>C、MTRR 66A>G、SHMT 1420C>T、chbetas 844ins68和RFC-1 80G>A等位基因和基因型频率，计算优势比（OR）。还测量了病例和对照组的红细胞叶酸水平，并比较了按基因型分层的红细胞叶酸水平中位数。MTHFR 677C >t变异未被证明是NTD感染孕妇的独立危险因素。MTHFR的第二个多态性1298A>C在NTD病例的母亲中较少观察到（OR [95% CI] = 0.57[0.33, 0.97]）。拥有化合物1298A>C和677C>T变异体显著增加了NTD妊娠的风险（TT/AC + TT/CC vs CC/AA OR [95% CI] = 6.56[1.10, 39.33]）。尽管在指数妊娠（17.6 +/- 12.6年）多年后进行了检测，但NTD母亲的红细胞叶酸水平持续较低（p = 0.001）。红细胞叶酸水平在MTHFR 677C >t变异存在时降低。(C) 2004爱思唯尔公司版权所有。
Previous studies have shown conflicting findings in linking polymorphic variation in folate-related genes to the risk of neural tube defect pregnancy. Recent evidence points to maternal genotype being important in determining NTD risk. A case-control study was undertaken in 97 mothers of NTD cases from the northern region of the UK. Pregnant controls (n = 190) from a regional DNA bank and non-pregnant controls (n = 100) from the same geographical area were recruited. MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, SHMT 1420C>T, CbetaS 844ins68, and RFC-1 80G>A allele and genotype frequencies were determined and odds ratios (OR) calculated. Erythrocyte folate levels for cases and controls were also measured and a comparison made of median erythrocyte folate levels stratified according to genotype. The MTHFR 677C>T variant was not shown to be an independent NTD risk factor in mothers of NTD-affected pregnancy. A second polymorphism in MTHFR, 1298A>C, was less frequently observed in mothers of NTD cases (OR [95% CI] = 0.57 [0.33, 0.97]). Possession of compound 1298A>C and 677C>T variants elevated risk of NTD pregnancy considerably (TT/AC + TT/CC vs CC/AA OR [95% CI] = 6.56 [1.10, 39.33]). Erythrocyte folate levels were persistently lower in NTD mothers (p = 0.001) despite assays being conducted many years after the index pregnancy (17.6 +/- 12.6 years). Erythrocyte folate levels were depressed in the presence of the MTHFR 677C>T variant. (C) 2004 Elsevier Inc. All rights reserved.