Liu Jian, Qi Jing, Yu Xiao, Zhu Jie, Zhang Lixia, Ning Qin, Luo Xiaoping
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatrics, Xiangyang Central Hospital, Xiangyang, China.
Department of Neurology, Xiangyang Central Hospital, Xiangyang, China.
J Neurol Sci. 2014 Feb 15;337(1-2):61-6. doi: 10.1016/j.jns.2013.11.017. Epub 2013 Nov 19.
We investigated the hypothesis that there are interactions between SNPs in folate metabolism pathway genes and environmental risk factors to the etiology of neural tube defects (NTDs).
In 602 Chinese families, 609 aborted fetus tissues or blood samples were collected from NTD individuals, and 1106 parental blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine administration before and during pregnancy were investigated. Case-parental control study and transmission/disequilibrium tests were performed according to environmental cofactor stratification.
Association between 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in all stratifications (all P<.05), and synergistic effects of no folate supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine-homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation significantly associated with NTDs (both P<.05), whereas the two genotypes alone did not significantly associate with NTDs (both P>.05).
MTHFR 677C>T genotype, especially in case of no folate supplementation and GDM, promotes NTD occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no folate supplementation contribute to the etiology of NTDs.
我们研究了如下假设，即叶酸代谢途径基因中的单核苷酸多态性（SNP）与神经管缺陷（NTDs）病因的环境危险因素之间存在相互作用。
在602个中国家庭中，从NTD个体收集了609份流产胎儿组织或血样，并检测1106份父母血样作为对照。我们分析了12个叶酸途径基因中的28个SNP。调查了叶酸补充、妊娠期糖尿病（GDM）以及妊娠前后的用药情况。根据环境辅助因子分层进行病例-父母对照研究和传递/不平衡检验。
在所有分层中，5,10-亚甲基四氢叶酸还原酶（MTHFR）677C>T与NTDs之间的关联均具有显著性（所有P<.05），并且未补充叶酸和GDM对NTDs的发生显示出协同作用。在GDM情况下，5-甲基四氢叶酸-同型半胱氨酸甲基转移酶（MTHM）501A>G以及在未补充叶酸情况下，甜菜碱-同型半胱氨酸甲基转移酶（BHMT）716G>A与NTDs显著相关（两者P<.05），而单独这两种基因型与NTDs无显著关联（两者P>.05）。
MTHFR 677C>T基因型，尤其是在未补充叶酸和GDM的情况下，会促进NTDs的发生。仅在GDM情况下的MTHM 501A>G以及仅在未补充叶酸情况下的BHMT 716G>A与NTDs的病因有关。
