神经管畸形与还原叶酸载体基因(RFC1 A80G)多态性及可疑危险因素的流行病学研究  

Epidemiological study on reduced folate carrier gene(RFC1 A80G) polymorphism and other risk factors of neural tube defects

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

机构地区：[1]北京大学生育健康研究所 [2]美国得克萨斯州农工大学环境与遗传医学中心生物科学技术研究所

出　　处：《北京大学学报（医学版）》2005年第4期341-345,共5页Journal of Peking University:Health Sciences

基　　金：国家重点基础研究发展规划项目基金(G1999055905)资助;国家"十五"科技攻关项目(2002BA709B11)资助~~

摘　　要：目的:探讨还原叶酸载体基因(Reducedfolatecarriergene,RFC1)A80G多态性及可疑危险因素对神经管畸形(neuraltubedefects,NTDs)的影响,为寻找NTDs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式反应(polymerasechainreactionrestrictionfragmentlengthpolymorphism,RFLPPCR)方法,对104个NTDs儿核心家庭和100个健康对照儿核心家庭RFC1A80G多态性进行检测,并且对家系成员RFC1基因型及其他因素进行单因素和多因素分析,在控制其他因素后观察RFC1基因型、母亲孕早期未增补叶酸对NTDs的独立影响,对NTDs杂合子父母G等位基因进行传递不平衡检验(transmission/disequilibriumtest,TDT)。结果:NTDs患儿G等位基因频率(64.42%)高于对照儿(52.53%),并且差异有统计学意义(χ2=5.9198,P<0.05);在单因素分析中,携带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),母亲孕早期未增补叶酸,生育NTDs的危险高于增补叶酸的母亲(OR=7.69,95%CI=2.86～21.75),其他危险因素(如父亲年龄、母亲孕早期发热、母亲自然流产史)在病例对照之间差异有统计学意义;在多因素Logistic回归分析中,子代RFC1GG基因型(OR=2.91,95%CI=1.35～6.30)、母亲孕早期未增补叶酸(OR=4.32,95%CI=1.62～11.55)、母亲孕早期发热(OR=3.22,95%CI=1.26～8.26)对NTDs的发病危险具有统计学意义。TDT结果显示,RFC1基因G等位基因与NTDs之间存在关联(χ2=5.236,P<0.05)。结论:在该研究人群中,RFC1GG基因型可能是NTDs发生的遗传易感基因之一,母亲孕早期未增补叶酸、发热对NTDs的发病也具有重要影响。Objective： To study the reduced folate carrier gene （RFC1） A80G polymorphism and other factors influence on children with neural tube defects （NTDs） and provide the epidemiological evidence for finding genetic marker of NTDs. Methods：RFC1 （A80G） genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism（RFLP-PCR） for blood DNA of 104 trios with NTDs-affected by child, and the 100 control families without child-affected by any birth defects. We performed the analysis of muhifactors logistic regression for RFC1 genotypes and other factors in order to investigate the RFC1 genotype of the nuclear families and maternal periconceptional folic acid supplementation influence on NTDs independently. Transmission/disequilibrium test （TDT） for the RFC1 genotype of NTDs and control pedigree were carried out. Results： The RFC1 G allele frequency of children with NTDs （64.42%） was higher than that of the control children （52.53%） ,and there was the significant difference between them （X^2= 5. 9198, P 〈0.05 ）. We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared with the AA genotype （95%CI = 1.04 -6.36）, The risk of mothers who did not take folic acid for having an NTDs-affected infants was7.69 （95% CI = 2.86 -21.75）. There were significant differences between cases and controls in the other risk factors, such as paternal age （ ≥30）, maternal fever during the early pregnancy, the history of maternal spontaneous abortion. In the logistic regression analysis, of muhifactors the three factors, for example, the offspring of the RFC1 GG genotype （OR =2.91,95% CI = 1.35 -6.30） , maternal periconceptional folic acid supplementation （OR =4.32,95% CI = 1.62 -11.55 ）, maternal fever during the early pregnancy, had the statistic significance for the risk of NTDs. There was the evidence of an association between G allele and the risk of the materal having a child with NTDs （ O

关 键 词：神经管缺损 叶酸 载体蛋白质类 多态性 限制性片段长度 

分 类 号：R742.89[医药卫生—神经病学与精神病学]