父母亚甲基四氢叶酸脱氢酶基因型对后代发生先天性心脏病的影响

Effect of parental 5,10-methylenetetrahydrofolate dehydrogenase genotypes on offspring congenital heart defect risk

目的 探讨父母亚甲基四氢叶酸 (CMTHFD)基因型对后代发生先天性心脏病 (CHD)的影响。 方法 选择辽宁省 192例CHD患者的父母作为病例组 ,同一地区年龄、性别匹配的 12 4名正常人的父母作为对照组 ,采用PCR RFLP方法检测其MTHFDG195 8A位点基因多态性 ,比较 2组的基因型频率和等位基因频率 ,并计算 2组父母生育纯合突变后代的概率的比值。 结果 CHD父母基因型频率和等位基因频率与对照组相比差异无显著性 (P >0 0 5 ) ;房间隔缺损母亲突变等位基因频率为 10 87% ,明显低于对照组 2 8 15 % (P <0 0 5 ) ,OR =0 31(95 %CI:0 0 9～ 0 84 ) ;房间隔缺损患者父母至少携带一个突变等位基因的比例为 4 3 4 8% ,亦明显低于对照组 6 9 6 4 % (P <0 0 5 ) ,OR =0 34(95 %CI:0 12～ 0 92 ) ;病例组和对照组父母可能生育的纯合突变胎儿占总胎儿数的比例分别为 5 17%和 7 0 4 % ,差异无显著性 (P >0 0 5 )。 结论 亲代 (尤其是母亲 )MTHFDG195 8A位点基因突变可降低后代房间隔缺损的危险性。

Objective To explore the effect of parental MTHFD genotypes on offspring CHD risk. Methods Biological parents of 192 patients having CHD were included in this study as case group in Liaoning province,and biological parents of 124 healthy subjects (age and gender matched)were simultaneously selected from the same geographic area as control.To all subjects,the gene polymorphism of MTHFD G1958A locus was examined with PCR-RFLP,to compare genotype distribution and allele frequency between case and control,and calculate the ratio of probabilities of the offspring being homozygotes(AA). Results No difference was observed when comparing genotype distribution and allele frequency between case and control.A allele frequency of arterial septal defect patients' mothers 10.87 % was significantly lower than that of control 28.15 %(P<0.05),with OR=0.31 (95 % CI:0.09～0.84),and no difference in other subgroups.Percentage of at least one parent carrying A allele in arterial septal defect subgroup (43.48 %) was significantly lower than that in control 69.64 %(P<0.05),with OR 0.34(95 % CI:0.12～0.92).There was no significant difference in percentage of offspring being homozygotes,with 5.17 % in case and 7.04 % in control. Conclusion MTHFD G1958A mutation in parents (particularly in mother) could decrease risk of arterial septal defect in offspring.