Verkleij-Hagoort Anna C, van Driel Lydi M J W, Lindemans Jan, Isaacs Aaron, Steegers Eric A P, Helbing Willem A, Uitterlinden André G, Steegers-Theunissen Régine P M
Department of Obstetrics, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Mol Genet Metab. 2008 May;94(1):112-9. doi: 10.1016/j.ymgme.2007.12.002. Epub 2008 Jan 15.
Maternal hyperhomocysteinemia is associated with congenital heart defects (CHDs) in the offspring. A low periconception vitamin B12 status is determined by genetic and lifestyle factors and causes hyperhomocysteinemia. We investigated methionine synthase reductase (MTRR) and transcobalamin II (TC) genes and maternal intake and serum concentrations of vitamin B12 in association with CHD risk. Seventeen months after the index-pregnancy, we studied 230 children with a CHD and 251 non-malformed children and their parents. Data were collected on current and periconception maternal vitamin supplement use and maternal dietary vitamin B12 intake of the month before the study moment. Blood samples were taken for the determination of MTRR A66G and TC C776G genotypes in families and maternal serum vitamin B12 concentrations. Transmission disequilibrium tests and univariate and multivariate analyses were applied. Allele transmissions were not significantly distorted. The MTRR and TC genotypes did not significantly affect CHD risk. Neither polymorphisms in mothers and/or children revealed significant interactions nor in combination with low vitamin B12 intake. Low maternal serum vitamin B12 combined with the maternal or child's MTRR 66 GG genotype resulted in odds ratios of 1.4 (95% confidence interval 0.6-3.5) and 1.3 (0.5-3.4), respectively. The TC 776 GG genotype in mothers and children revealed risk estimates of 2.2 (0.7-7.1) and 1.9 (0.5-7.4), respectively. In conclusion, MTRR 66 GG and TC 776 GG genotypes in mothers and children may contribute to the risk of CHDs, particularly when the maternal vitamin B12 status is low. The future enlargement of our sample size might demonstrate significant associations.
母体高同型半胱氨酸血症与后代先天性心脏病（CHD）有关。受孕前维生素B12水平低由遗传和生活方式因素决定，并导致高同型半胱氨酸血症。我们研究了甲硫氨酸合成酶还原酶（MTRR）和转钴胺素II（TC）基因以及母体维生素B12的摄入量和血清浓度与CHD风险的关系。在索引妊娠17个月后，我们研究了230名患有CHD的儿童和251名无畸形儿童及其父母。收集了关于当前和受孕前母体维生素补充剂使用情况以及研究前一个月母体膳食维生素B12摄入量的数据。采集血样以测定家庭中MTRR A66G和TC C776G基因型以及母体血清维生素B12浓度。应用了传递不平衡检验以及单变量和多变量分析。等位基因传递没有明显扭曲。MTRR和TC基因型对CHD风险没有显著影响。母亲和/或儿童的多态性单独或与低维生素B12摄入量联合均未显示出显著的相互作用。母体血清维生素B12水平低与母亲或儿童的MTRR 66 GG基因型相结合时，比值比分别为1.4（95%置信区间0.6 - 3.5）和1.3（0.5 - 3.4）。母亲和儿童的TC 776 GG基因型的风险估计值分别为2.2（0.7 - 7.1）和1.9（0.5 - 7.4）。总之，母亲和儿童的MTRR 66 GG和TC 776 GG基因型可能会增加CHD的风险，特别是当母体维生素B12水平较低时。未来扩大样本量可能会显示出显著的关联。
