糖尿病患者同型半胱氨酸及其代谢相关酶基因多态性与颈动脉内膜—中膜厚度的关系  

Relationship between Genetic Polymorphisms of Homocysteine Metablism Related Enzymes and Carotid Intima-Media Thickness in Type 2 Diabetic Patients

作　　者：潘琦[1] 郭立新[1] 初明峰[1] 满永[2] 孙明晓[1] 李铭[1] 刘小萍[1] 

机构地区：[1]卫生部北京医院内分泌科,北京市100730 [2]卫生部北京医院老年医学研究所,北京市100730

出　　处：《中国动脉硬化杂志》2005年第2期195-198,共4页Chinese Journal of Arteriosclerosis

基　　金：国家科技部十五攻关课题 (2 0 0 2BA70 2B0 1 )

摘　　要：目的　探讨2型糖尿病患者同型半胱氨酸水平及其代谢过程的相关酶甲基四氢叶酸还原酶基因C6 77T和胱硫醚缩合酶基因T833C位碱基突变与颈动脉内膜—中膜厚度的关系。方法　用酶联免疫吸附法测定同型半胱氨酸水平,采用聚合酶链反应—限制片长多态性方法检测甲基四氢叶酸还原酶基因C6 77T基因型多态性,用扩增阻滞突变体系法检测胱硫醚缩合酶基因T833C多态性,用彩色多普勒检查颈动脉内膜—中膜厚度。结果　糖尿病颈动脉内膜—中膜厚度增厚组甲基四氢叶酸还原酶基因和胱硫醚缩合酶基因构成与糖尿病颈动脉内膜—中膜厚度正常组及对照组存在统计学差异(P <0 .0 5 )。三组甲基四氢叶酸还原酶基因和胱硫醚缩合酶基因突变者血浆同型半胱氨酸均高于无基因突变者。糖尿病组甲基四氢叶酸还原酶基因和胱硫醚缩合酶基因突变者颈动脉内膜—中膜厚度明显高于无基因突变者。结论　同型半胱氨酸代谢过程中关键酶基因变异可造成相关酶活性改变,进而出现高同型半胱氨酸血症促进糖尿病动脉粥样硬化的形成。甲基四氢叶酸还原酶基因C6 77T点突变和胱硫醚缩合酶基因T833C点突变可能是糖尿病合并血管病变发病的重要遗传因素。Aim To investigate the relationship of plasma homocysteine (Hcy) level and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine β-synthase (CBS) T833C related to homocysteine metabolism with carotid intima-media thickness (IMT) in type 2 diabetic patients. Methods Plasma Hcy level was measured by enzyme linked immunosordent assay (ELISA). MTHFR genetic C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), and CBS T833C polymorphism was determined by amplification refractory mutation system (ARMS) method, carotid intimal-medial wall thickness was determined by the use of the duplex ultrasonography. Results The genotype frequency of diabetics with thicked IMT was different from that of diabetic patients with normal IMT and control groups (P<0.05). Plama homocysteine levels were markly higher in patients with MTHFR or CBS genetic mutation than those in patients without mutation in each group. IMT in MTHFR or CBS genetic mutation were thicker than those in patients without mutation in diabetic group. Conclusion Mutation of MTHFR or CBS can both cause the elevation of plasma homocysteine level so as to induce the onset of arteriosclosis in diabetics. Their genetic mutations are possibly the important mechanism of macroangiopathy in diabetics.

关 键 词：内科学 糖尿病血管病变的分子机制 聚合酶链反应-限制片长多态性 同型半胱氨酸 基因突变 内膜-中膜厚度 

分 类 号：R5[医药卫生—内科学]