亲代蛋氨酸合酶基因变异对子代发生先天性心脏病的影响

目的:初步探讨亲代蛋氨酸合酶(MS)基因变异与子代先天性心脏病(CHD)表型的关系.方法:通过出生缺陷登记卡选择辽宁省192名CHD患者(其中男93人,女99人)及其生物学父母(核心家庭)作为病例组,另选取同地区无出生缺陷病史及家族史的104名正常人(男60人,女44人)及其生物学父母作为对照组,进行MS基因A2756G位点多态性检测(PCR-RFLP法),比较两组间亲代基因变异差异及病例组核心家庭内等位基因的传递不平衡现象.结果:病例组与对照组母亲的基因型分布和等位基因频率差异无显著性(P>0.05),病例组父亲( )等位基因频率(5.0%)低于对照组(9.1%,P＝0.060),其子代罹患CHD的比值比(OR)为0.53(95%CI为0.25～ 1.09);两组父母基因型组合差异无显著性;不同类型CHD组与对照组父母A2756G位点基因型构成比差异亦无显著性;等位基因传递不平衡分析显示,突变等位基因( )在CHD核心家庭中存在传递不平衡现象,即父母将等位基因( )传给CHD患者的比例低于(-),其OR值为0.26(95%CI为0.11～0.60).结论:亲代MS基因A2756G位点变异与子代CHD的发生相关,其突变等位基因( )可能降低子代CHD的危险性.

Effects of methionine synthase gene variation in parents on occurence of congenital heart disease in offspring

OBJECTIVE: To investigate the relations of methionine synthase (MS) gene variation in parents with congenital heart disease (CHD) phenotype in offspring. METHODS: We selected 192 CHD patients (93 males and 99 females) and their biological parents (nuclear families) in Liaoning Province as case group, and 104 normal people (60 males and 44 females) and their parents without family history of birth defects as control group. For all subjects the MS gene A2756G locus polymorphism was examined by PCR-RFLP method. The data were analyzed to compare the difference of gene variation between the case parents and controls, and to assess the genetic disequilibrium in the CHD nuclear families. RESULTS: The MS genotype distribution and allele frequencies of the case mothers were not different significantly from those of the control group (P>0.05). The frequency of allele (+) in the case fathers (5.0%) was lower than that of the control (9.1%, P=0.060). The odds ratio (OR) was 0.53 (95% CI: 0.25-1.09). There was no difference in parents' genotype combination between the two groups. The analysis of allele transmission indicated that mutation allele (+) transmission disequilibrium existed in CHD nuclear families. The percentage of allele (+) transmitted from the parents was lower than (-) with being OR 0.26 (95% CI: 0.11-0.60). CONCLUSION: The study shows that the MS gene variation at A2756G locus in parents is associated with occurrence of CHD in offspring, and the mutation allele (+) in parents might be related with the decrease of CHD risk in offspring.