A parental case control study on the association between reduced folate carrier gene polymorphism and neural tube defects

目的对神经管畸形(NTDs)发病危险和还原叶酸载体基因(RFC1)A80G多态性进行关联研究,为寻找NTDs的遗传易感标志物提供流行病学依据.方法采用RFLP-PCR方法,对104例NTDs儿及其父母和99名正常儿童及其父母的外周血DNA进行RFC1第80位SNP检测,对核心家庭基因型进行病例对照研究,对NTDs杂合子父母G等位基因进行传递不平衡检验(TDT).结果NTDs儿G等位基因频率高于对照儿,OR值为1.64(95%CI:1 08～2.49);GG基因型的患儿发生NTDs危险高于AA基因型(OR=2.56,95%CI:1.04～6 36);TDT结果显示,RFC1等位基因G与NTDs之间存在关联(x2=5.2364,P＜0.05),携带G等位基因发生NTDs的危险是非携带者的1.56倍(95%CI:1.07～2.28).结论发现在中国人群中RFC1基因多态性与NTDs存在关联,初步表明该基因G等位基因可能是NTDs发生的遗传易感基因之一.To study the association between reduced folate carrier gene (RFC1 A80G) polymorphism and the risk for child with neural tube defects (NTDs), and to provide epidemiological evidence for the existence of NTDs genetic marker.RFC1 (A80G) genotypes were detected using RFLP-PCR for blood DNA of 104 families with NTDs-affected children and 100 control families with no history of child-affected birth defects. Case-control study and transmission/disequilibrium test(TDT) for the RFC1 genotype of NTDs pedigree were carried out.The G allele frequency of children with NTDs was higher than that of controls when compared to A allele( OR = 1. 64, 95% CI :1.08-2.49). The offspring of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (OR = 2.56, 95% CI: 1.04-6.36) in our study population. There was evidence of association between G allele and the risk of parent having a child with NTDs (OR = 1.56, 95% CI: 1.07-2.28) in the TDT analysis.Our findings indicated that there was potential association between offspring RFC1 GG genotype and the risk of NTDs, and the G allele was a possible susceptible gene marker for an increased NTDs risk in the Chinese population.国家重点基础研究发展计划(973计划); 科技部专项基金PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)09665-6682