叶酸代谢酶基因多态性与新生儿出生缺陷中的相关研究
|
摘要
目的探讨叶酸代谢酶基因多态性在新生儿出生缺陷的中的应用及相关研究。方法选择2016年3月-2018年2月正常孕检的孕妇146例作为对象,利用eppdndorf核酸定量仪测定孕妇白细胞中DNA含量,利用测序级扩增仪扩增MHFR的C677T、A66G位点相应的基因片段,双相测序法完成PCR产妇的测定;采用全自动生化分析仪测定孕妇同型半胱氨酸(Hcy)水平,采用免疫发光法测定叶酸(FA)及维生素B12水平;根据基因测定结果分为观察组(n=87例,中度风险或高风险)和对照组(n=59,无风险或低风险),观察组每天补充叶酸800μg,对照组每天补充叶酸400μg,连续进行3个月干预;统计并记录两组干预后神经管畸形、唇腭裂、先天性心脏病、四肢畸形、唐氏综合征发生率。结果正常孕检的孕妇均顺利完成基因分型检测,MHFR的C677T基因分型中排在前两位的分别为CC、CT;MHFR的A66G基因分型中排在前两位的分别为AA和AG;基因C677T中CT、TT分型下Hcy水平,低于CC分型(P<0.05);C677T中CT、TT分型下FA、维生素B12水平,高于CC分型(P<0.05);A66G中AA分型下Hcy水平,高于AG、GG分型(P<0.05);A66G中AA分型下FA、维生素B12水平,均低于AG、GG分型(P<0.05);观察组与对照组干预前Hcy、FA及维生素B12水平差异无统计学意义(P>0.05);观察组与对照组干预后Hcy水平,均低于干预前(P<0.05);观察组与对照组干预后FA、维生素B12水平,均高于干预前(P<0.05);观察组与对照组孕妇分娩后新生儿神经管畸形、唇腭裂、先天性心脏病、四肢畸形、唐氏综合征发生率差异无统计学意义(P>0.05)。结论叶酸代谢酶基因多态性中MHFR的C677T/T、66A/A能直接参与新生儿出生缺陷,加强叶酸代谢酶基因多态性、Hcy测定根据叶酸利用能力针对性补充叶酸能降低出生缺陷发生率。
Objective:To investigate the application and related research of folate metabolic enzyme gene polymorphism in neonatal birth defects.Methods:A total of 146 pregnant women with normal pregnancy tests from March 2016 to February 2018 were enrolled.The DNA content of leukocytes in pregnant women was determined by eppdndorf nucleic acid quantitation.The C677 T and A66 G loci of MHFR were amplified by sequencing-grade amplification instrument.Gene fragment,duplex phase sequencing method to complete the determination of PCR maternal;automatic biochemical analyzer to determine the level of homocysteine(Hcy)in pregnant women,immunofluorescence method for determination of folic acid(FA)and vitamin B12 levels;Divided into observation group(n=87 cases,moderate risk or high risk)and control group(n=59,no risk or low risk),the observation group was supplemented with folic acid 800 ug per day,and the control group was supplemented with folic acid 400 ug per day for 3 consecutive days.Monthly intervention;statistics and recorded the incidence of neural tube defects,cleft lip and palate,congenital heart disease,limb deformity,and Down syndrome after intervention.Results:The pregnant women with normal pregnancy test successfully completed the genotyping test.The top two of the C677 T genotypes of MHFR were CC and CT respectively.The top two A66 G genotypes of MHFR were AA.And AG;gene C677 T in the CT,TT classification Hcy level,lower than CC classification(P<0.05);C677T in CT,TT classification FA,vitamin B12 level,higher than CC classification(P<0.05)The level of Hcy in AA was higher than that in AG and GG(P<0.05).The levels of FA and vitamin B12 in A66 G were lower than those in AG and GG(P<0.05).There were no significant differences in Hcy,FA and vitamin B12 levels between the control group and the control group(P>0.05).The Hcy levels in the observation group and the control group were lower than those before the intervention(P<0.05).The observation group and the control group The levels of FA and vitamin B12 were higher than those before intervention(P<0.05).The incidence of neonatal neural tube defects,cleft lip and palate,congenital heart disease,limb malformation and Down syndrome after delivery in the observation group and the control group.The difference was not statistically significant(P>0.05).Conclusion:C677T/T and 66A/A of MHFR in folate metabolism gene polymorphism can directly participate in neonatal birth defects,strengthen folate metabolic enzyme gene polymorphism,and Hcy determination can reduce birth defects according to folic acid utilization ability.Incidence.
Objective:To investigate the application and related research of folate metabolic enzyme gene polymorphism in neonatal birth defects.Methods:A total of 146 pregnant women with normal pregnancy tests from March 2016 to February 2018 were enrolled.The DNA content of leukocytes in pregnant women was determined by eppdndorf nucleic acid quantitation.The C677 T and A66 G loci of MHFR were amplified by sequencing-grade amplification instrument.Gene fragment,duplex phase sequencing method to complete the determination of PCR maternal;automatic biochemical analyzer to determine the level of homocysteine(Hcy)in pregnant women,immunofluorescence method for determination of folic acid(FA)and vitamin B12 levels;Divided into observation group(n=87 cases,moderate risk or high risk)and control group(n=59,no risk or low risk),the observation group was supplemented with folic acid 800 ug per day,and the control group was supplemented with folic acid 400 ug per day for 3 consecutive days.Monthly intervention;statistics and recorded the incidence of neural tube defects,cleft lip and palate,congenital heart disease,limb deformity,and Down syndrome after intervention.Results:The pregnant women with normal pregnancy test successfully completed the genotyping test.The top two of the C677 T genotypes of MHFR were CC and CT respectively.The top two A66 G genotypes of MHFR were AA.And AG;gene C677 T in the CT,TT classification Hcy level,lower than CC classification(P<0.05);C677T in CT,TT classification FA,vitamin B12 level,higher than CC classification(P<0.05)The level of Hcy in AA was higher than that in AG and GG(P<0.05).The levels of FA and vitamin B12 in A66 G were lower than those in AG and GG(P<0.05).There were no significant differences in Hcy,FA and vitamin B12 levels between the control group and the control group(P>0.05).The Hcy levels in the observation group and the control group were lower than those before the intervention(P<0.05).The observation group and the control group The levels of FA and vitamin B12 were higher than those before intervention(P<0.05).The incidence of neonatal neural tube defects,cleft lip and palate,congenital heart disease,limb malformation and Down syndrome after delivery in the observation group and the control group.The difference was not statistically significant(P>0.05).Conclusion:C677T/T and 66A/A of MHFR in folate metabolism gene polymorphism can directly participate in neonatal birth defects,strengthen folate metabolic enzyme gene polymorphism,and Hcy determination can reduce birth defects according to folic acid utilization ability.Incidence.
引文
[1]马秋华,冯锐金,李红英,等.曲靖地区新生儿主要出生缺陷流行病学及干血斑筛查的应用研究[J].中国优生与遗传杂志,2018,26(04):75-77+69.
[2]袁春雷,王冬娥,叶贵诚,等.叶酸代谢相关基因及血清同型半胱氨酸与出生缺陷的相关性[J].实用医学杂志,2016,32(11):1860-1863.
[3]周登诗,黄芳,范大志,钟进.同型半胱氨酸、叶酸和维生素B12水平与不良妊娠结局的相关性分析[J].中国计划生育学杂志,2017,25(09):624-626.
[4]Fang Y,Zhang R,Zhi X,et al.Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China[J].Childs Nervous System,2018,34(4):1-5.
[5]李芳兵,张丹丹,高琴,等.叶酸吸收代谢途径基因多态性与新生儿出生缺陷的相关性分析[J].河北医药,2017,39(18):2768-2770.
[6]宫彩莹,肖慧.沈阳市浑南区医院出生缺陷监测报告[J].中国优生与遗传杂志,2015,23(07):79.
[7]尹保民,杨小红,曾淑兰.叶酸代谢障碍与出生缺陷的关系探讨[J].中国优生与遗传杂志,2017,25(10):75-77.
[8]钟欢欣.衢州地区孕期叶酸代谢障碍相关基因及叶酸干预与出生缺陷的相关性研究[D].浙江中医药大学,2018.
[9]徐小惠,鲁衍强,李瑛,等.湖北省英山县汉族女性MTHFR和MTRR的遗传多态性分析[J].中国妇幼健康研究,2016,27(2):252-255.
[10]杨丰美,于艳,张丽萍.育龄女性MTHFR基因多态性与HCY关系的研究[J].川北医学院学报,2016,31(2):205-207.
[11]袁春雷,王冬娥,叶贵诚,等.叶酸代谢相关基因及血清同型半胱氨酸与出生缺陷的相关性[J].实用医学杂志,2016,32(11):1860-1863.
[12]Christensen K E,Bahous R H,Hou W,et al.Low Dietary Folate Interacts with MTHFD1 Synthetase Deficiency in Mice,a Model for the R653Q Variant,to Increase Incidence of Developmental Delays and Defects[J].Journal of Nutrition,2018,148(4):501.
[13]潘伟,冯晓萍,俞磊.叶酸代谢相关酶系基因多态性与不良孕史的相关性研究[J].中国妇产科临床杂志,2017,18(04):332-336.
[14]刘念,阎炯,杨林.叶酸代谢相关酶基因多态性与不良孕产关系的研究[J].中国计划生育学杂志,2015,23(05):318-320.
[2]袁春雷,王冬娥,叶贵诚,等.叶酸代谢相关基因及血清同型半胱氨酸与出生缺陷的相关性[J].实用医学杂志,2016,32(11):1860-1863.
[3]周登诗,黄芳,范大志,钟进.同型半胱氨酸、叶酸和维生素B12水平与不良妊娠结局的相关性分析[J].中国计划生育学杂志,2017,25(09):624-626.
[4]Fang Y,Zhang R,Zhi X,et al.Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China[J].Childs Nervous System,2018,34(4):1-5.
[5]李芳兵,张丹丹,高琴,等.叶酸吸收代谢途径基因多态性与新生儿出生缺陷的相关性分析[J].河北医药,2017,39(18):2768-2770.
[6]宫彩莹,肖慧.沈阳市浑南区医院出生缺陷监测报告[J].中国优生与遗传杂志,2015,23(07):79.
[7]尹保民,杨小红,曾淑兰.叶酸代谢障碍与出生缺陷的关系探讨[J].中国优生与遗传杂志,2017,25(10):75-77.
[8]钟欢欣.衢州地区孕期叶酸代谢障碍相关基因及叶酸干预与出生缺陷的相关性研究[D].浙江中医药大学,2018.
[9]徐小惠,鲁衍强,李瑛,等.湖北省英山县汉族女性MTHFR和MTRR的遗传多态性分析[J].中国妇幼健康研究,2016,27(2):252-255.
[10]杨丰美,于艳,张丽萍.育龄女性MTHFR基因多态性与HCY关系的研究[J].川北医学院学报,2016,31(2):205-207.
[11]袁春雷,王冬娥,叶贵诚,等.叶酸代谢相关基因及血清同型半胱氨酸与出生缺陷的相关性[J].实用医学杂志,2016,32(11):1860-1863.
[12]Christensen K E,Bahous R H,Hou W,et al.Low Dietary Folate Interacts with MTHFD1 Synthetase Deficiency in Mice,a Model for the R653Q Variant,to Increase Incidence of Developmental Delays and Defects[J].Journal of Nutrition,2018,148(4):501.
[13]潘伟,冯晓萍,俞磊.叶酸代谢相关酶系基因多态性与不良孕史的相关性研究[J].中国妇产科临床杂志,2017,18(04):332-336.
[14]刘念,阎炯,杨林.叶酸代谢相关酶基因多态性与不良孕产关系的研究[J].中国计划生育学杂志,2015,23(05):318-320.