还原叶酸载体基因多态性与先天性心脏病和唇腭裂关联的研究

目的 检验还原叶酸载体基因(RFC1)A80G多态性与先天性心脏病(CHD)和唇腭裂之间的关联,为寻找CHD和唇腭裂危险因素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67个CHD患儿家庭、82个唇腭裂患儿家庭和100个正常儿童家庭成员的外周血DNA进行RFC1第80位SNP检测,利用核心家庭标本进行以家庭为基础的关联检验(FBAT),并分析了子代RFC1基因型与母亲孕期前后增补叶酸的相互作用。结果 不增补叶酸的母亲生育CHD儿的危险高于增补叶酸的母亲(OR=2 68,95％CI:1 14-6 41),即母亲孕期未增补叶酸与CHD发生危险的关联有统计学意义(x2=6.213,P=0 013);在FBAT检验中,RFC1 G等位基因与CHD发病危险有统计学关联(Z=2 140,P<0 05),表明RFC1 G等位基因可能是CHD发病的遗传易感基因,未发现唇腭裂与RFC1之间的统计学关联。结论 RFC1 G等位基因可能是CHD发生的遗传易感基因之一,子代RFC1基因GG或GA基因型、母亲孕期叶酸缺乏可能增加CHD的发病危险。

Study on the association between reduced folate gene polymorphism and congenital heart defects and cleft lip with or without cleft palate

Objective To study the association between reduced folate carrier gene (RFC1 ) polymorphism and congemtal heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP. Methods RFC1 (A80G) genotype was detecled using RFLP-PCR for blood DNA o{ the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional suppleraentation of folic acid. Results Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did ( OR = 2 68,95% CI: l 14-6 41). There was a stalisucal associauon between the risk of CHD and maternal periconceptional fohc acid supplementation (x2 =6.213,P<0.05) In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2. 140, P<0.05) while G allele of RFC1(A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid. Conclusion Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offsprmg with GG,GA genotype and maternal periconceptional folic acid deficiency