神经管畸形患儿还原叶酸载体基因和叶酸之间交互作用(英文)  

Interaction between maternal periconceptional supplementat ion of folic acid and reduced folate carrier gene polymorphism of neural tube defects

作　　者：裴丽君[1] 朱慧萍 李智文[1] 张卫[1] 任爱国[1] 朱江辉[1] 李竹[1] 

机构地区：[1]北京大学生育健康研究所,卫生部生育健康重点实验室100083 [2]Institute of Biosciences and Technology, Texas A & M University System Hea lth Science Center, Houston, U.S.A.

出　　处：《中华医学遗传学杂志》2005年第3期284-287,共4页Chinese Journal of Medical Genetics

基　　金：国家重点基础研究专项基金(G1999055905);国家"十五攻关"项目(2002BA709B11)~~

摘　　要：目的探讨神经管畸形(neuraltubedefects,NTDs)患儿还原叶酸载体基因(reducedfolatecarriergene,RFC1)A80G多态性与母亲孕早期未增补叶酸之间的关联性,为寻找NTDs危险因素的遗传易感标志物提供流行病学依据。方法采用限制性片段长度多态性聚合酶链反应方法,对104个NTDs患儿及其母亲和100名正常儿童及其母亲的外周血DNA进行RFC1第80位单核苷酸多态性检测,通过病例对照研究,调查了后代RFC1A80G基因型与母亲孕期前后增补叶酸之间的基因环境交互作用。结果RFC1GG基因型的子代发生NTDs危险高于AA基因型子代(OR=2.56,95%CI=1.04～6.36);母亲孕早期不增补叶酸,生育NTDs的危险高于增补叶酸的母亲(OR=7.69,95%CI=2.86～21.75);母亲孕期未增补叶酸,其子代GG基因型,发生NTDs的危险是AA基因型的3.30倍(95%CI=1.15～9.65);在叶酸和RFC1基因交互作用研究中,母亲未增补叶酸和子代GG基因型同时存在,发生NTDs的危险是8.80(95%CI=2.86～29.82),交互作用系数为1.45。结论在中国人群中,RFC1GG基因型可能是NTDs发生的遗传易感基因之一,子代RFC1GG基因型与母亲孕期叶酸缺乏之间存在交互作用,可能增加NTDs的发病危险。Objective To search the interaction between re duced folate carrier gene ( RFC1 A80G) polymorphism of children with neural tube defects (NTDs) and maternal periconceptional no supplementation of folic acid. T he purpose is to provide the epidemiological evidence for finding genetic marker of NTDs. Methods RFC1 (A80G) genotype was detected using PCR- restricted fragment length polymorphism for the blood DNA of 104 tri os with NTDs-affected child, and 100 control families with non-malformed contr ol children. The authors investigated the gene-en vironment interactions between the offspring RFC1 genotype and mater nal periconc eptional folic acid supplementation through a case-control study. Resul ts It was observed that the offspring with the GG genotype were associa ted wi th a 2.56-fold increased risk of NTDs when compared to those with the AA genoty pe (OR=2.56; 95%CI=1.04-6.36) in this population under investigation. The risk of mothers who did not tak e folic acid for having an NTDs-affected infants was 7.69 (95%CI=2.86-21.75). Among the mothers who did not utilize folic acid supplements, the NTDs risk was 3.30 (95%CI=1.15-9.65) for offspring with the GG genotype, compared to the referenc e (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR=8.80, 95%CI=2.86-29.82), compared to “offspring with AA or GA genotype” and “maternal folic acid use”, the i nter active coefficient being 1.45. Conclusion The above findings in dicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in Ch inese population, and there is a potential gene-nutrient interaction between o ffspring RFC1 GG genotype and maternal periconceptional intake of fo lic acid on the risk of NTDs. However,the sample size of this study was limited, a larger sa mple of population-based study is required to pursue the initial observation.

关 键 词：神经管畸形 小儿 还原叶酸 载体基因 叶酸 交互作用 遗传因素 

分 类 号：R725.9[医药卫生—儿科]