母体生化代谢和营养状况与胎儿神经管畸形的相关研究
发布时间：2019-03-25 06:54
【摘要】：【目的】本实验采用流行病学、营养学和生物化学相结合的方法，通过了解母体叶酸、维生素B12、同型半胱氨酸、一碳基团中间代谢产物、DNA甲基化指数与胎儿神经管畸形发生的相关性，为预防和治疗胎儿神经管畸形提供科学依据，并为开展神经管畸形发生中环境-遗传因素相互作用的研究提供新思路。 【方法】选择山西省神经管畸形高发地区(榆社、壶关、宁武等)的孕妇作为本次试验的研究对象，病例组52例，孕12-20周B超诊断为NTDs，另一组为对照组52例，孕12-20周因各种原因需要终止妊娠进行引产，经病理解剖证明胎儿正常。对两组孕妇进行问卷调查,包括年龄和孕周、既往妊娠史、家族史、此次妊娠情况等。检测两组孕妇体内叶酸、维生素B12、同型半胱氨酸、SAM、SAH、DNA甲基化指数水平，经两独立样本秩和检验、两独立样本t检验，比较其在病例组及对照组孕妇中是否存在统计学差异。结合ROC统计学方法，比较他们在神经管畸形发病风险评估和预测中的作用。通过ROC曲线找出各物质的截点，采用Logistic回归得到OR值。 【结果】 1．经χ2检验、秩和检验，孕妇的一般情况(如年龄、职业、文化程度、饮食情况、孕周等)之间无统计学差异。 2．病例组及对照组孕妇叶酸、维生素B12、一碳基团中间代谢物、DNA甲基化指数有显著差异性(P0.05)。两组孕妇同型半胱氨酸无统计学差异(P0.05)。 3．DNA甲基化指数诊断神经管畸形的ROC曲线下面积及约登指数最大。余依次为SAH、SAM、叶酸、维生素B12，tHcy的曲线下面积及跃登指数最低，但无统计学意义(P0.05)，余物质有统计学意义(P0.05)。4．孕妇叶酸7.6nmol/L，维生素B12169pmol/L，tHcy≥11.3umol/L，SAM49nmol/L，SAH≥11nmol/L，DNA甲基化指数4.4是神经管畸形的危险因素。低叶酸水平(7.6的)孕妇发生神经管畸形的危险度是正常叶酸水平(≥7.6)的孕妇的6倍(95%CI为2.2~15.6)，具有统计学意义(OR=5.95，P0.05)。同样，低Vit B12、高tHcy、低SAM、高SAH、低SAM/SAH均为是神经管畸形的危险因素，均有统计学意义(OR值分别为3.20、2.56、11.11、479.40和625，均P0.05)。 【结论】 1．病例组和对照组孕妇在一般情况上是均衡的。 2．叶酸、维生素B12、SAM、SAH、DNA甲基化指数在病例组与对照组孕妇中存在统计学差异，两组之间各物质含量有所不同。 3．DNA甲基化指数诊断神经管畸形的价值最高，可用于疾病标记物的筛选和评价。 4．叶酸、维生素B12缺乏可能通过改变母体一碳基团代谢水平影响胎儿DNA甲基化，最终导致神经管畸形的形成。
[Abstract]:[objective] to study maternal folic acid, vitamin B12, homocysteine and intermediate metabolites of one carbon group by means of epidemiology, nutrition and biochemistry. The correlation between DNA methylation index and the occurrence of fetal neural tube malformations provides a scientific basis for the prevention and treatment of fetal neural tube malformations, and provides a new idea for the study of the interaction between environmental and genetic factors in the occurrence of neural tube malformations. [methods] pregnant women in Shanxi province with high incidence of neural tube malformations (Yushe, Huguan, Ningwu, etc.) were selected as the subjects of this experiment. 52 cases in the case group, 52 cases in the B-ultrasound group diagnosed as NTDs, at 12 weeks after pregnancy, and 52 cases in the control group were diagnosed by B-ultrasound at 12 weeks of gestation. After 12 weeks gestation, the pregnancy was induced for various reasons, and the fetus was proved to be normal by pathological anatomy. Two groups of pregnant women were investigated by questionnaire, including age and week of pregnancy, previous pregnancy history, family history, pregnancy status and so on. The levels of folic acid, vitamin B12, homocysteine and SAM,SAH,DNA methylation index in two groups of pregnant women were detected by rank sum test of two independent samples and t test of two independent samples. To compare whether there is statistical difference in the pregnant women between the patient group and the control group. ROC statistical methods were used to compare their role in risk assessment and prediction of neural tube malformations. The cut-off point of each substance was found by ROC curve and OR value was obtained by Logistic regression. [results] 1. By 蠂 2 test, rank sum test, there was no statistical difference among the general conditions of pregnant women (such as age, occupation, education, diet, gestational weeks, etc.). 2. There were significant differences in folic acid, vitamin B12, monocarbon intermediate metabolite and DNA methylation index between the two groups (P0.05). There was no significant difference in homocysteine between the two groups (P0.05). The area under the ROC curve and the Joden index were the largest in the diagnosis of neural tube malformations by 3.DNA methylation index. SAH,SAM, folic acid, vitamin B12 and tHcy had the lowest area under the curve and leapfrog index (P0.05), but there was no statistical significance (P0.05), but the rest substances had statistical significance (P0.05). 4. Pregnant women folic acid 7.6nmol / L, Vitamin B12169pmol / L, tHcyc 11.3umol / L, SAM49nmol / L, SAH 11nmol / L, DNA methylation index 4.4 were the risk factors of neural tube malformation. The risk of neural tube malformation in pregnant women with low folate level (7.6) was 6 times higher than that in normal pregnant women (鈮，
本文编号：2446733
[Abstract]:[objective] to study maternal folic acid, vitamin B12, homocysteine and intermediate metabolites of one carbon group by means of epidemiology, nutrition and biochemistry. The correlation between DNA methylation index and the occurrence of fetal neural tube malformations provides a scientific basis for the prevention and treatment of fetal neural tube malformations, and provides a new idea for the study of the interaction between environmental and genetic factors in the occurrence of neural tube malformations. [methods] pregnant women in Shanxi province with high incidence of neural tube malformations (Yushe, Huguan, Ningwu, etc.) were selected as the subjects of this experiment. 52 cases in the case group, 52 cases in the B-ultrasound group diagnosed as NTDs, at 12 weeks after pregnancy, and 52 cases in the control group were diagnosed by B-ultrasound at 12 weeks of gestation. After 12 weeks gestation, the pregnancy was induced for various reasons, and the fetus was proved to be normal by pathological anatomy. Two groups of pregnant women were investigated by questionnaire, including age and week of pregnancy, previous pregnancy history, family history, pregnancy status and so on. The levels of folic acid, vitamin B12, homocysteine and SAM,SAH,DNA methylation index in two groups of pregnant women were detected by rank sum test of two independent samples and t test of two independent samples. To compare whether there is statistical difference in the pregnant women between the patient group and the control group. ROC statistical methods were used to compare their role in risk assessment and prediction of neural tube malformations. The cut-off point of each substance was found by ROC curve and OR value was obtained by Logistic regression. [results] 1. By 蠂 2 test, rank sum test, there was no statistical difference among the general conditions of pregnant women (such as age, occupation, education, diet, gestational weeks, etc.). 2. There were significant differences in folic acid, vitamin B12, monocarbon intermediate metabolite and DNA methylation index between the two groups (P0.05). There was no significant difference in homocysteine between the two groups (P0.05). The area under the ROC curve and the Joden index were the largest in the diagnosis of neural tube malformations by 3.DNA methylation index. SAH,SAM, folic acid, vitamin B12 and tHcy had the lowest area under the curve and leapfrog index (P0.05), but there was no statistical significance (P0.05), but the rest substances had statistical significance (P0.05). 4. Pregnant women folic acid 7.6nmol / L, Vitamin B12169pmol / L, tHcyc 11.3umol / L, SAM49nmol / L, SAH 11nmol / L, DNA methylation index 4.4 were the risk factors of neural tube malformation. The risk of neural tube malformation in pregnant women with low folate level (7.6) was 6 times higher than that in normal pregnant women (鈮，
本文编号：2446733
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