中国人群母亲5,10-亚甲基四氢叶酸还原酶基因C677T多态性与子代神经管畸形易感性关系的Meta分析
|
摘要
目的探讨母亲5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与子代神经管畸形(NTDs)发生的关联性及关联强度。方法制定检索策略和文献纳入排除标准,检索主题词为中英文形式的"MTHFR"和"叶酸代谢通路"和"基因多态性或SNP"和"神经管畸形/神经管缺陷"并追踪参考文献中的相关研究,纳入可以从文献中直接获得或计算得出OR值及95%CI病例-对照研究的中英文文献。系统检索从建库至2017年7月5日在中国生物医学文献数据库、中国期刊全文数据库、万方数据库、重庆维普中文科技期刊全文数据库、Pub Med数据库和Web of Science发表的有关中国人群母亲MTHFR C677T位点多态性与子代NTDs易感性的病例-对照研究文献、学位论文及引文。提取相应数据并采用Rev Man 5.3软件进行Meta分析。结果 13篇文献纳入分析,包括病例组1500例,对照组1654例。在TT基因型vs CC基因型、TT+CT基因型vs CC基因型、等位基因T vs等位基因C合并OR(95%CI)分别为1.94(1.58~2.39)、1.65(1.39~1.98)和1.39(1.26~1.54)。结果显示,在中国人群母亲MTHFR基因C677T位点多态性与子代NTDs发生之间存在较大的关联性。结论中国人群母亲MTHFR基因C677T位点多态性是子代NTDs发病的重要危险因素之一,基于MTHFR多态性检测的孕期叶酸补充指导和检测将是进一步降低新生儿出生缺陷的重要手段。
Objective To explore the association between maternal MTHFR gene polymorphism( C677T) and neural tube defects in offspring through Meta-analysis in China. Method CNKI,Pub Med,Web of Science,Chinese Wan Fang Data databases,CBM,VIP for published articles were searched from the time of Database establishment to July 5 th 2017. The search strategy was based on combinations of the English and/or Chinese keywords,‘MTHFR'and ‘folate pathway'and ‘polymorphism'or ‘SNP'and‘NTDs or Neural Tube Defects'. References of reviews and retrieved studies were also scanned. All the case-control studies about MTHFR gene C677T polymorphism and susceptibility of neural tube defect were collected,which were fulfilled the followinginclusion criteria: case-control study and cohort study design, presentation of data necessary for calculating odds ratios( ORs). Data were extracted from studies and analyzed by Rev Man 5. 3 software. Results A total of 13 papers were selected,including1500 patients and 1654 controls. Meta-analysis result showed that the combined odds ratio values of neural tube defect for offspring with maternal TT,TT + CT and T allele genotypes were 1. 94,1. 65 and 1. 39, respectively. Conclusion The present Meta-analysis suggests that MTHFR C677T is significantly associated with maternal risk for NTDs in the Chinese population, supplemental folic acid supplementation based on MTHFR polymorphisms will be an important means to further reduce the birth defects of newborns.
Objective To explore the association between maternal MTHFR gene polymorphism( C677T) and neural tube defects in offspring through Meta-analysis in China. Method CNKI,Pub Med,Web of Science,Chinese Wan Fang Data databases,CBM,VIP for published articles were searched from the time of Database establishment to July 5 th 2017. The search strategy was based on combinations of the English and/or Chinese keywords,‘MTHFR'and ‘folate pathway'and ‘polymorphism'or ‘SNP'and‘NTDs or Neural Tube Defects'. References of reviews and retrieved studies were also scanned. All the case-control studies about MTHFR gene C677T polymorphism and susceptibility of neural tube defect were collected,which were fulfilled the followinginclusion criteria: case-control study and cohort study design, presentation of data necessary for calculating odds ratios( ORs). Data were extracted from studies and analyzed by Rev Man 5. 3 software. Results A total of 13 papers were selected,including1500 patients and 1654 controls. Meta-analysis result showed that the combined odds ratio values of neural tube defect for offspring with maternal TT,TT + CT and T allele genotypes were 1. 94,1. 65 and 1. 39, respectively. Conclusion The present Meta-analysis suggests that MTHFR C677T is significantly associated with maternal risk for NTDs in the Chinese population, supplemental folic acid supplementation based on MTHFR polymorphisms will be an important means to further reduce the birth defects of newborns.
引文
[1]WALD N J,SNEDDON J,DENSEM J,et al.Prevention of neural tube defects:results of the medical research council vitamin study MRC vitamin study group[J].Lancet,1991,338:142-147.
[2]MARINI N J,HOFFMANN T J,LAMMER E J,et al.A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis[J].Plo S One,2011,6(11):e28408.
[3]GOYETTE P,SUMNER J S,MILOS R,et al.Human methylenetetrahydrofolate reductase:isolation of c DNA mapping and mutation identification[J].Nat Genet,1994,7(2):195-200.
[4]FROSST P,BLOM H J,MILOS R,et al.A candidate genetic risk factor for vascular disease:a common mutation in methylenetetrahydrofolate reductase[J].Nat Genet,1995,10(1):111-114.
[5]ESKES T K.Neural tube defects,vitamins and homocysteine[J].Eur J Pediatr,1998,157(2):S149-S141.
[6]ROSENQUIST T H,FINNELL R H.Genes,folate and homocysteine in embryonic development[J].Proc Nutr Soc,2001,60(1):53-61.
[7]TAKIMOTO H,Mito N,UMEGAKI K,et al.Relationship between dietary folate intakes,maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan[J].Eur J Nutr,2007,46(5):300-306.
[8]MILLS J L,Mc PARTLIN J M,KIRKE P N,et al.Homocysteine metabolism in pregnancies complicated by neural tube defects[J].Lancet,1997,13(11-13):994-995.
[9]郑冬梅,薛雅丽,金焰,等.母亲的MTHFR基因多态性位点与NTD发生的关系[J].中国优生与遗传杂志,1999(6):81-82.
[10]郭晓霞,高原原,詹思延,等.5,10-亚甲基四氢叶酸还原酶多态性和神经管畸形的病例对照研究[J].中华疾病控制杂志,2000,4(3):217-219.
[11]朱慧萍,李竹.中国人MTHFR基因多态性与神经管畸形遗传易感性[J].遗传,2000,22(4):236-238.
[12]王浩.神经管畸形与同型半胱氨酸代谢相关基因多态性的病例对照研究[D].太原:山西医科大学,2004.
[13]王刚华.血浆HCY及其代谢酶基因多态性与神经管畸形的关系[D].太原:山西医科大学,2006.
[14]郑梅玲,王刚华,张桂林.血浆同型半胱氨酸(HCY)及其代谢酶基因多态性与神经管畸形的关系[J].中国生育健康杂志,2007,14(4):158-161.
[15]邬晋芳,杨华,张欣,等.生育过神经管缺陷儿的妇女MTHFR基因C677T多态性与血浆Hcy水平测定[J].中国优生与遗传杂志,2008(12):15-16.
[16]王芳,杨艳芳,李佩珍.山西省神经管畸形影响因素的病例对照研究[J].中华流行病学杂志,2008,29(8):771-774.
[17]SHANG Y,ZHAO H,NIU B,et al.Correlation of polymorphism of MTHFRs,and RFC-1,genes with neural tube defects in China[J].Birth Defects Res A,2008,82(1):3-7.
[18]CHEN X,GUO J,LEI Y,et al.Global DNA hypomethylation is associated with NTD-affected pregnancy:A case-control study[J].Birth Defects Res A,2010,88(7):575-581.
[19]YU Y,WANG F,BAO Y,et al.Association between MTHFR gene polymorphism and NTDs in Chinese Han population[J].Int J Clin Exp Med,2014,7(9):2901-2906.
[20]LIU J,ZHANG Y,JIN L,et al.Variants in maternal COMT and MTHFR genes and risk of neural tube defects in offspring[J].Metab Brain Dis,2015,30(2):507-514.
[21]石鸥燕,吴波,张瑞苹,等.叶酸代谢关键酶基因多态性与儿童神经管缺陷的相关性[J].中华实用儿科临床杂志,2016,31(10):779-782.
[22]李克深,郑冬梅,薛雅丽,等.MTHFR基因C677T多态与神经管缺陷及先兆子痫关系的研究[J].中华医学遗传学杂志,2000,17(2):76-78.
[23]申丽丽.母亲MTHFR C677T、CBS T 833C、G919A基因型与胎儿NTDs发生的关系[D].长沙:中南大学,2008.
[24]裴利花.同型半胱氨酸及其代谢酶基因多态性与神经管畸形发生的关系[D].长沙:中南大学,2011.
[25]邓朝霞.母亲MTHFR、e NOS基因多态性及环境因素与NTDs关系的研究[D].遵义:遵义医学院,2014.
[26]中华人民共和国卫生部.中国出生缺陷防治报告(2012)[R].北京:中华人民共和国卫生部,2012.
[27]ROSS M E.Gene-environment interactions,folate metabolism and the embryonic nervous system[J].Wiley Interdiscip Rev Syst Biol Med,2010,2(4):471-480.
[28]ZEISEL S H.Importance of methyl donors during reproduction[J].Am J Clin Nutr,2009,89(2):673S-677S.
[29]YAN L,LIN Z,YAN L,et al.Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offspring:evidence from 25 case-control studies[J].Plos One,2012,7(10):e41689.
[30]李军,史海龙,帖红莉.MTHFR基因多态性检测在神经管缺陷干预中的应用[J].中国生育健康杂志,2008,14(4):163-164.
[31]CARTER T C,PANGILINAN F,TROENDLE J F,et al.Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population[J].Am J Med Genet A,2011,155A(1):14.
[32]KIRKE P N,MILLS J L,MOLLOY A M,et al.Impact of the MTHFR C677T polymorphism on risk of neural tube defects:case-control study[J].BMJ,2004,328(7455):1535-1536.
[33]BERRY R J,LI Z,ERICKSON J D,et al.Prevention of neural-tube defects with folic acid in China[J].New Engl J Med,1999,341(200):1485-1490.
[34]Institute of Medicine(US)Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate,Other B Vitamins,and Choline.Dietary reference intakes for thiamin,riboflavin,niacin,vitamin B6,folate,vitamin B12,pantothenic acid,biotin,and choline[J].Trends Food Sci Tech,2000,11(8):296-297.
[35]HERNANDEZ R.Use of folic acid for prevention of spina bifida and other neural tube defects-1983-1991[J].MMWR,1991,40(30):514.
[2]MARINI N J,HOFFMANN T J,LAMMER E J,et al.A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis[J].Plo S One,2011,6(11):e28408.
[3]GOYETTE P,SUMNER J S,MILOS R,et al.Human methylenetetrahydrofolate reductase:isolation of c DNA mapping and mutation identification[J].Nat Genet,1994,7(2):195-200.
[4]FROSST P,BLOM H J,MILOS R,et al.A candidate genetic risk factor for vascular disease:a common mutation in methylenetetrahydrofolate reductase[J].Nat Genet,1995,10(1):111-114.
[5]ESKES T K.Neural tube defects,vitamins and homocysteine[J].Eur J Pediatr,1998,157(2):S149-S141.
[6]ROSENQUIST T H,FINNELL R H.Genes,folate and homocysteine in embryonic development[J].Proc Nutr Soc,2001,60(1):53-61.
[7]TAKIMOTO H,Mito N,UMEGAKI K,et al.Relationship between dietary folate intakes,maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan[J].Eur J Nutr,2007,46(5):300-306.
[8]MILLS J L,Mc PARTLIN J M,KIRKE P N,et al.Homocysteine metabolism in pregnancies complicated by neural tube defects[J].Lancet,1997,13(11-13):994-995.
[9]郑冬梅,薛雅丽,金焰,等.母亲的MTHFR基因多态性位点与NTD发生的关系[J].中国优生与遗传杂志,1999(6):81-82.
[10]郭晓霞,高原原,詹思延,等.5,10-亚甲基四氢叶酸还原酶多态性和神经管畸形的病例对照研究[J].中华疾病控制杂志,2000,4(3):217-219.
[11]朱慧萍,李竹.中国人MTHFR基因多态性与神经管畸形遗传易感性[J].遗传,2000,22(4):236-238.
[12]王浩.神经管畸形与同型半胱氨酸代谢相关基因多态性的病例对照研究[D].太原:山西医科大学,2004.
[13]王刚华.血浆HCY及其代谢酶基因多态性与神经管畸形的关系[D].太原:山西医科大学,2006.
[14]郑梅玲,王刚华,张桂林.血浆同型半胱氨酸(HCY)及其代谢酶基因多态性与神经管畸形的关系[J].中国生育健康杂志,2007,14(4):158-161.
[15]邬晋芳,杨华,张欣,等.生育过神经管缺陷儿的妇女MTHFR基因C677T多态性与血浆Hcy水平测定[J].中国优生与遗传杂志,2008(12):15-16.
[16]王芳,杨艳芳,李佩珍.山西省神经管畸形影响因素的病例对照研究[J].中华流行病学杂志,2008,29(8):771-774.
[17]SHANG Y,ZHAO H,NIU B,et al.Correlation of polymorphism of MTHFRs,and RFC-1,genes with neural tube defects in China[J].Birth Defects Res A,2008,82(1):3-7.
[18]CHEN X,GUO J,LEI Y,et al.Global DNA hypomethylation is associated with NTD-affected pregnancy:A case-control study[J].Birth Defects Res A,2010,88(7):575-581.
[19]YU Y,WANG F,BAO Y,et al.Association between MTHFR gene polymorphism and NTDs in Chinese Han population[J].Int J Clin Exp Med,2014,7(9):2901-2906.
[20]LIU J,ZHANG Y,JIN L,et al.Variants in maternal COMT and MTHFR genes and risk of neural tube defects in offspring[J].Metab Brain Dis,2015,30(2):507-514.
[21]石鸥燕,吴波,张瑞苹,等.叶酸代谢关键酶基因多态性与儿童神经管缺陷的相关性[J].中华实用儿科临床杂志,2016,31(10):779-782.
[22]李克深,郑冬梅,薛雅丽,等.MTHFR基因C677T多态与神经管缺陷及先兆子痫关系的研究[J].中华医学遗传学杂志,2000,17(2):76-78.
[23]申丽丽.母亲MTHFR C677T、CBS T 833C、G919A基因型与胎儿NTDs发生的关系[D].长沙:中南大学,2008.
[24]裴利花.同型半胱氨酸及其代谢酶基因多态性与神经管畸形发生的关系[D].长沙:中南大学,2011.
[25]邓朝霞.母亲MTHFR、e NOS基因多态性及环境因素与NTDs关系的研究[D].遵义:遵义医学院,2014.
[26]中华人民共和国卫生部.中国出生缺陷防治报告(2012)[R].北京:中华人民共和国卫生部,2012.
[27]ROSS M E.Gene-environment interactions,folate metabolism and the embryonic nervous system[J].Wiley Interdiscip Rev Syst Biol Med,2010,2(4):471-480.
[28]ZEISEL S H.Importance of methyl donors during reproduction[J].Am J Clin Nutr,2009,89(2):673S-677S.
[29]YAN L,LIN Z,YAN L,et al.Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offspring:evidence from 25 case-control studies[J].Plos One,2012,7(10):e41689.
[30]李军,史海龙,帖红莉.MTHFR基因多态性检测在神经管缺陷干预中的应用[J].中国生育健康杂志,2008,14(4):163-164.
[31]CARTER T C,PANGILINAN F,TROENDLE J F,et al.Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population[J].Am J Med Genet A,2011,155A(1):14.
[32]KIRKE P N,MILLS J L,MOLLOY A M,et al.Impact of the MTHFR C677T polymorphism on risk of neural tube defects:case-control study[J].BMJ,2004,328(7455):1535-1536.
[33]BERRY R J,LI Z,ERICKSON J D,et al.Prevention of neural-tube defects with folic acid in China[J].New Engl J Med,1999,341(200):1485-1490.
[34]Institute of Medicine(US)Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate,Other B Vitamins,and Choline.Dietary reference intakes for thiamin,riboflavin,niacin,vitamin B6,folate,vitamin B12,pantothenic acid,biotin,and choline[J].Trends Food Sci Tech,2000,11(8):296-297.
[35]HERNANDEZ R.Use of folic acid for prevention of spina bifida and other neural tube defects-1983-1991[J].MMWR,1991,40(30):514.