蛋氨酸合酶基因变异与先天性心脏病的关系

目的　蛋氨酸合酶 (MS)是同型半胱氨酸代谢关键酶 ,旨在了解其与先天性心脏病(CHD)发生的关系。方法　选择 186名多种类型CHD患者 (0～ 31岁 ,性别比约为 1∶1)作为病例组 ,以同地区且年龄、性别匹配的 10 3名正常人作为对照 ,进行MS基因A2 75 6G位点多态性分析 (PCR RFLP法 )及血清叶酸、维生素B12 (VB12 )水平的测定 (放射免疫法 )。结果　显示本研究人群中存在MS基因A2 75 6G位点杂合突变 (+ - ) ,但未检出纯合突变 (+ +)基因型 ;其中对照组 (+ - )基因型和 (+)等位基因的频率分别为 10 7%和 5 3% ,低于报道的白种人及日本人变异频率 ;病例组 (+ - )基因型和 (+)等位基因的频率为 9 1%和 4 6 % ,与对照组相比其基因型构成差异无显著性 ;(+ - )基因型罹患CHD的比值比 (OR)为 0 84 (95 %可信区间 ,0 35～ 2 0 1) ;不同类型CHD与对照组的基因型构成亦无明显差异 ;此外病例组血清VB12 水平低于对照组 (336 6 6pmol L和 4 6 5 72pmol L) ,但无统计学意义 (P >0 0 5 ) ;两组的叶酸水平无明显差异 ;病例组不同基因型叶酸、VB12 水平差异亦无显著性。结论　MS基因A2 75 6G位点变异与CHD及血清叶酸、VB12 水平无明显关联 ,还有待进一步研究。

Relations of methionine synthase gene variation with congenital heart disease

Objective Methionine synthase (MS) is the key enzyme in the homocysteine metabolism. To investigate the relations of MS gene variation with occurrence of congenital heart disease (CHD).Methods 186 CHD patients (0-31 years old) were selected as case group and 103 normal population as control. For all subjects the gene polymorphism at MS A2756G locus was analysed by PCR-RFLP method, and the serum folic acid/vitamin B 12 levels were detected by radio-immunity assay.Results The heterozygotes ( /-) were detected in the subjects but without homozygotes ( / ). In control group the frequencies of ( /-) genotype and ( ) allele were 10.7% and 5.3%, lower than Caucasian and Japanese population. In case group the frequencies of ( /-) genotype and ( ) allele were 9.1% and 4.6%, without significantly different from control. The odds ratio of ( /-) genotype was 0.84 (0.35, 2.01). The genotype distributions in different types of CHD were also not apparently different with control. The serum vitamin B 12 level was decreased in case group compared with control (336.66pmol/L vs 465.72pmol/L, P>0.05), but the serum folic acid level no different. Also there were not significant difference for folic acid/vitamin B 12 levels between different genotypes in case group. Conclusion The results indicated that there was not apparent association between MS gene A2756G locus variation with CHD and serum folic acid/vitamin B 12 levels. It need further investigations.