母體生化代謝和營(yíng)養(yǎng)狀況與胎兒神經(jīng)管畸形的相關(guān)研究
發(fā)布時(shí)間：2019-03-25 06:54
【摘要】：【目的】本實(shí)驗(yàn)采用流行病學(xué)、營(yíng)養(yǎng)學(xué)和生物化學(xué)相結(jié)合的方法，通過(guò)了解母體葉酸、維生素B12、同型半胱氨酸、一碳基團(tuán)中間代謝產(chǎn)物、DNA甲基化指數(shù)與胎兒神經(jīng)管畸形發(fā)生的相關(guān)性，為預(yù)防和治療胎兒神經(jīng)管畸形提供科學(xué)依據(jù)，并為開(kāi)展神經(jīng)管畸形發(fā)生中環(huán)境-遺傳因素相互作用的研究提供新思路。 【方法】選擇山西省神經(jīng)管畸形高發(fā)地區(qū)(榆社、壺關(guān)、寧武等)的孕婦作為本次試驗(yàn)的研究對(duì)象，病例組52例，孕12-20周B超診斷為NTDs，另一組為對(duì)照組52例，孕12-20周因各種原因需要終止妊娠進(jìn)行引產(chǎn)，經(jīng)病理解剖證明胎兒正常。對(duì)兩組孕婦進(jìn)行問(wèn)卷調(diào)查,包括年齡和孕周、既往妊娠史、家族史、此次妊娠情況等。檢測(cè)兩組孕婦體內(nèi)葉酸、維生素B12、同型半胱氨酸、SAM、SAH、DNA甲基化指數(shù)水平，經(jīng)兩獨(dú)立樣本秩和檢驗(yàn)、兩獨(dú)立樣本t檢驗(yàn)，比較其在病例組及對(duì)照組孕婦中是否存在統(tǒng)計(jì)學(xué)差異。結(jié)合ROC統(tǒng)計(jì)學(xué)方法，比較他們?cè)谏窠?jīng)管畸形發(fā)病風(fēng)險(xiǎn)評(píng)估和預(yù)測(cè)中的作用。通過(guò)ROC曲線找出各物質(zhì)的截點(diǎn)，采用Logistic回歸得到OR值。 【結(jié)果】 1．經(jīng)χ2檢驗(yàn)、秩和檢驗(yàn)，孕婦的一般情況(如年齡、職業(yè)、文化程度、飲食情況、孕周等)之間無(wú)統(tǒng)計(jì)學(xué)差異。 2．病例組及對(duì)照組孕婦葉酸、維生素B12、一碳基團(tuán)中間代謝物、DNA甲基化指數(shù)有顯著差異性(P0.05)。兩組孕婦同型半胱氨酸無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。 3．DNA甲基化指數(shù)診斷神經(jīng)管畸形的ROC曲線下面積及約登指數(shù)最大。余依次為SAH、SAM、葉酸、維生素B12，tHcy的曲線下面積及躍登指數(shù)最低，但無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)，余物質(zhì)有統(tǒng)計(jì)學(xué)意義(P0.05)。4．孕婦葉酸7.6nmol/L，維生素B12169pmol/L，tHcy≥11.3umol/L，SAM49nmol/L，SAH≥11nmol/L，DNA甲基化指數(shù)4.4是神經(jīng)管畸形的危險(xiǎn)因素。低葉酸水平(7.6的)孕婦發(fā)生神經(jīng)管畸形的危險(xiǎn)度是正常葉酸水平(≥7.6)的孕婦的6倍(95%CI為2.2~15.6)，具有統(tǒng)計(jì)學(xué)意義(OR=5.95，P0.05)。同樣，低Vit B12、高tHcy、低SAM、高SAH、低SAM/SAH均為是神經(jīng)管畸形的危險(xiǎn)因素，均有統(tǒng)計(jì)學(xué)意義(OR值分別為3.20、2.56、11.11、479.40和625，均P0.05)。 【結(jié)論】 1．病例組和對(duì)照組孕婦在一般情況上是均衡的。 2．葉酸、維生素B12、SAM、SAH、DNA甲基化指數(shù)在病例組與對(duì)照組孕婦中存在統(tǒng)計(jì)學(xué)差異，兩組之間各物質(zhì)含量有所不同。 3．DNA甲基化指數(shù)診斷神經(jīng)管畸形的價(jià)值最高，可用于疾病標(biāo)記物的篩選和評(píng)價(jià)。 4．葉酸、維生素B12缺乏可能通過(guò)改變母體一碳基團(tuán)代謝水平影響胎兒DNA甲基化，最終導(dǎo)致神經(jīng)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，
本文編號(hào)：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，
本文編號(hào)：2446733
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