Relton Caroline L, Wilding Craig S, Laffling Alison J, Jonas Pat A, Burgess Terry, Binks Keith, Tawn E Janet, Burn John
Paediatric and Lifecourse Epidemiology Research Group, School of Clinical Medical Sciences (Child Health), Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne NE2 4LP, UK.
Mol Genet Metab. 2004 Apr;81(4):273-81. doi: 10.1016/j.ymgme.2003.12.010.
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.
以往的研究在叶酸相关基因的多态性变异与神经管缺陷妊娠风险的关联上得出了相互矛盾的结果。近期证据表明，母亲的基因型在决定神经管缺陷风险方面很重要。在英国北部地区，对97名神经管缺陷患儿的母亲进行了一项病例对照研究。招募了来自区域DNA库的怀孕对照者（n = 190）和来自同一地理区域的未怀孕对照者（n = 100）。测定了亚甲基四氢叶酸还原酶（MTHFR）677C>T、MTHFR 1298A>C、甲硫氨酸合成酶还原酶（MTRR）66A>G、丝氨酸羟甲基转移酶（SHMT）1420C>T、胱硫醚β-合成酶（CbetaS）844ins68以及还原型叶酸载体-1（RFC-1）80G>A等位基因和基因型频率，并计算了优势比（OR）。还测量了病例组和对照组的红细胞叶酸水平，并对根据基因型分层的红细胞叶酸水平中位数进行了比较。在受神经管缺陷影响妊娠的母亲中，MTHFR 677C>T变异未被证明是独立的神经管缺陷风险因素。MTHFR中的另一种多态性，即1298A>C，在神经管缺陷病例的母亲中较少见（OR [95%置信区间]=0.57 [0.33, 0.97]）。拥有1298A>C和677C>T复合变异会显著增加神经管缺陷妊娠的风险（TT/AC+TT/CC与CC/AA相比，OR [95%置信区间]=6.56 [1.10, 39.33]）。尽管在本次妊娠指数后多年（17.6±12.6年）进行了检测，但神经管缺陷母亲的红细胞叶酸水平持续较低（p = 0.001）。存在MTHFR 677C>T变异时，红细胞叶酸水平会降低。
