国际生殖健康/计划生育杂志

国际生殖健康/计划生育 ›› 2011, Vol. 30 ›› Issue (3): 169-172.

• 论著 • 上一篇    下一篇

神经管畸形儿及其父母还原叶酸载体基因多态性的 FBAT关联研究


裴丽君, 朱慧萍, 刘建蒙, 叶荣伟, 李智文, 任爱国, 郑晓瑛   

  1. 100871 北京大学人口研究所（裴丽君，郑晓瑛），Dell Pediatric Research Institute，Department of Nutritional Sciences, School of Human Ecology，University of Texas at Austin， U. S. A.（朱慧萍），北京大学生育健康研究所（刘建蒙，叶荣伟，李智文，任爱国）
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2011-05-15 发布日期:2011-05-15
  • 通讯作者: 郑晓瑛

Family-Based Association Test for Reduced Folate Carrier Gene Polymorphism of Parent and Offspring with Neural Tube Defects

PEI Li-jun， ZHU Hui-ping， LIU Jian-meng， YE Rong-wei， LI Zhi-wen， REN Ai-guo， ZHENG Xiao-ying   

  1. Institute of Population Research， Peking University， Beijing 100871， China（PEI Li-jun， ZHENG Xiao-ying）； Dell Pediatric Research Institute， Department of Nutritional Sciences, School of Human Ecology， University of Texas at Austin， U.S.A.（ZHU Hui-ping）； Institute of Reproductive Health，Peking University， Beijing 100083， China（LIU Jian-meng， YE Rong-wei， LI Zhi-wen， REN Ai-guo）
  • Received:1900-01-01 Revised:1900-01-01 Published:2011-05-15 Online:2011-05-15
  • Contact: ZHENG Xiao-ying

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摘要： 目的：探讨神经管畸形（neural tube defects， NTDs）儿及其父母的还原叶酸载体基因（reduced folate carrier gene， RFC1）A80G多态性在NTDs发生危险中的作用，为探讨NTDs遗传易感标记物提供流行病学依据。方法：应用聚合酶链反应-限制性片段长度多态性（PCR?鄄RFLP）技术，检测104例NTDs儿及其父母和100例健康对照儿及其父母的RFC1 A80G多态性，利用病例-父母对照研究中传递/不平衡检验（TDT检验）和以家系为基础的关联检验（FBAT检验）分析NTDs儿的父母RFC1基因A80G多态性与NTDs发生危险的关联，及其在子代中传递的作用强度。结果：患儿父母均为杂合子GA/GA的比例高达36.36%，NTDs患儿成为纯合子GG的概率为25%时具有统计学意义（P＜0.05），表明患儿接受父母遗传的G等位基因的概率均为25%，并有发生NTDs危险的可能。NTDs的TDT检验结果显示，患儿父母传递等位基因G的危险性是传递等位基因A危险性的1.56 倍（95%CI：1.07~2.28），认为该基因在亲代和NTDs子代间存在传递失衡现象。FBAT检验中，不论显性模型还是隐性模型，均未发现等位基因G与NTDs的发生危险存在关联，该结果与上述病例-父母对照研究TDT检验结果不一致。结论：虽然TDT检验中G等位基因与NTDs发生危险有关，但FBAT检验未发现G等位基因与NTDs发生危险存在关联，应进一步加大核心家系数量验证该结果。

关键词: 先天畸形, 神经管缺损, 膜转运蛋白质类, 还原叶酸载体基因, 以家系为基础的关联检验

Abstract: Objective：To search the risk of reduced folate carrier gene（RFC1 A80G） polymorphism of parent and offspring with neural tube defects（NTDs）. The purpose is to provide the epidemiological evidence for finding genetic marker of NTDs. Methods: RFC1（A80G） genotype were detected using RFLP-PCR for blood DNA of the 104 triads with NTDs-affected child, and the 100 control families without child-affected birth defects. We investigated the association between the risk of NTDs and parental and offspring’s RFC1 genotype through a case?-parental control study and Family-based association test（FBAT）. Results: The parental heterozygosis GA/GA accounted for 36.36%; Twenty?-five percent of probability of offspring’s becoming homozygote GG which was associated with NTDs（P<0.05）， indicating that mother and father transmitted G allele to offspring by the probability. The G allele frequency of offspring with NTDs was higher than that of controls when compared to A allele（OR=1.56, 95% CI: 1.07-2.28）. There was evidence of association between G allele and the risk of parent having a child with NTDs in the case?-parental control study. However, there was no association between G allele and the risk of NTDs in the FBAT. Conclusions: Our findings indicated that there was no significant association between the risk of NTDs and offspring G allele in FBAT although there was potential association in case?-parental control study． However, the sample size of this study was limited, a larger samples of population?-based study is required to pursue the initial observation.

Key words: Congenital abnormalities, Neural tube defects, Membrane transport proteins, Reduced folate carrier gene, Family?-Based Association Test