先天性心脏病核心家庭血清同型半胱氨酸水平及相关基因多态性研究  

Study of serum Hcy and polymorphisms of Hcy metabolic enzymes in 192 families affected by congenital heart disease

作　　者：李勇[1] 成君[1] 朱文丽[1] 刀京晶[1] 闫丽盈[1] 李孟忆[1] 李书琴[2] 

机构地区：[1]北京大学公共卫生学院营养与食品卫生学系,北京100083 [2]中国医科大学第二医院

出　　处：《北京大学学报（医学版）》2005年第1期75-80,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金重点项目 (30 0 30 1 2 0 ) ;教育部教育振兴行动计划特殊专项"九八五"工程 (2 0 0 1 1 4 )资助~~

摘　　要：目的 :了解MTHFRC6 77T、MSA2 75 6G、MTHFDG195 8A和CBS 84 4ins6 8bp位点在中国北方正常人群中的基因型分布 ,并评价单一或复合位点基因变异与叶酸、维生素B12 、同型半胱氨酸 (Hcy)水平及先天性心胖病(CHD)的关系。方法 :选择辽宁省 192例CHD患者及其父母作为病例组 ,同一地区年龄、性别匹配的 12 4名正常人及其父母作为对照组 ,采用PCR RFLP方法检测其基因型 ,放射免疫法和荧光偏振免疫法测定血清叶酸、维生素B12 和Hcy水平 ,比较两组差异。 结果 :中国北方正常人群中 ,这四个位点的突变等位基因频率分别为MTHFR5 1.18% ,MS 7.5 8% ,MTHFD 2 4 .32 % ,CBS插入频率 2 .36 % ;CBS 84 4ins6 8bp位点杂合型频率病例组明显高于对照组 (子代为 12 .5 7%和 2 .97% ,父亲为 10 .88%和 3.0 9% ,母亲为 11.5 4 %和 1.0 2 % ) ,子代的OR值为 4 .70(95 %CI 1.34～ 2 5 .15 ) ,父亲的OR值为 3.83(95 %CI 1.0 5～ 2 0 .98) ,母亲的OR值为 12 .6 5 (95 %CI 1.92～5 32 .4 7) ,其他三个位点两组差异无统计学意义 ;MTHFR、CBS和MTHFD三个位点联合基因变异的母亲、MTHFR和CBS两个位点联合基因变异的母亲 (OR =8.4 4 ,95 %CI:1.2 3～ 36 2 .2 6 )。Objective: To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and to assess the association of single or combined gene mutations with folic acid, Vit.B 12 , Hcy levels and CHD. Methods: 192 patients having CHD and their biological parents in Liaoning province registered as birth defects were included in this study as case group, and 124 healthy subjects (age and gender matched) and their biological parents were simultaneously selected from the same geographic area as control. To all subjects, the gene polymorphism at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci was examined with PCR-RFLP.The serum folic acid and homocysteine (Hcy) level were analyzed with Radio-immunoassay or fluorescence polarization immunoassay (FPIA). Results: In healthy Chinese living in northern China, the mutant allele frequencies of these four loci were MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, and CBS insertion 2.36%, respectively. The heterozygosity of CBS 844 ins68bp was more prevalent in case than in control (12.57% vs 2.97% in children, 10.88% vs 3.09% in father and 11.54% vs 1.02% in mother, respectively), and yielded an odds ratio (OR) of 4.70 (95% CI 1.34- 25.15) in children, 3.83 (95% CI 1.05-20.98) in fathers and 12.65 (95% CI 1.92-532.47) in mothers. There is no existed significant difference at the other three loci. The percents of mothers with MTHFR, CBS and MTHFD gene polymorphisms, of mothers with MTHFR and CBS being polymorphisms (OR=8.44,95%CI 1.23-362.26), of mothers with MTHFD and CBS being polymorphisms in case were higher than those in control. Serum folic acid levels of mothers and fathers in case were significantly higher than those of counterparts in control. Serum Hcy level of mothers in case was higher than that of counterparts in control without significant difference. Homozygous mutation at MTHFR and MTHFD loci made serum folic acid and Vit.B 12 levels slightly decreased and serum Hcy le

关 键 词：先天性心脏缺损 高半胱氨酸 多态现象 系谱 叶酸 

分 类 号：R541.1[医药卫生—心血管疾病]