DDAH2基因-449G/C多态性及ADMA水平与2型糖尿病合并动脉粥样硬化的相关性  

The Correlation of Dimethyl Arginine Dimethylamine Hydrolase 2 Gene- 449G/C Polymorphism and Plasma Asymmetric Dimethylarginine Levels with Atherosclerosis in Type 2 Diabetes

作　　者：石柔[1] 杨晶晶[1] 刘华[2] 陈洪艳[3] 雷又鸣[4] 宋滇平[1] 

机构地区：[1]昆明医科大学第一附属医院糖尿病科,云南省昆明市650032 [2]昆明医科大学第一附属医院检验科,云南省昆明市650032 [3]昆明医科大学第一附属医院超声科,云南省昆明市650032 [4]昆明医科大学第一附属医院干疗科,云南省昆明市650032

出　　处：《中国动脉硬化杂志》2015年第9期896-901,共6页Chinese Journal of Arteriosclerosis

基　　金：云南省应用基础研究(昆医联合专项)基金(2014FZ014)资助;云南省教育厅科学研究基金(2012Y023)资助

摘　　要：目的探讨二甲基精氨酸二甲胺水解酶2(DDAH2)基因-449G/C多态性及非对称性二甲基精氨酸(ADMA)水平与2型糖尿病合并动脉粥样硬化的相关性。方法运用聚合酶链反应限制性片段长度多态性技术对146例健康对照者和238例2型糖尿病患者[其中未合并动脉粥样硬化组(D0组)80例,合并早期动脉粥样硬化组(D1组)71例,合并中晚期动脉粥样硬化组(D2组)87例]的DDAH2基因-449G/C多态性进行检测,应用酶联免疫吸附法检测血浆ADMA浓度,并比较分析各组间基因型、等位基因频率及相关临床指标。结果 2型糖尿病合并动脉粥样硬化组(D1+D2组)DDAH2基因-449G/G基因型频率及G等位基因频率高于D0组(P<0.05)。2型糖尿病组中,DDAH2基因-449G/G基因型携带者具有较高的ADMA水平(P<0.05);ADMA水平在D1+D2组>D0组,且D2>D1>D0组(P<0.01)。Logistic回归显示,血浆ADMA是2型糖尿病合并动脉粥样硬化发生与发展的危险因素,DDAH2基因-449G/G基因型是2型糖尿病合并动脉粥样硬化发生的危险因素。结论在云南地区汉族人群中,DDAH2基因-449G/G基因型可能是2型糖尿病合并动脉粥样硬化发生的遗传易感因子,该基因型携带者具有较高的ADMA水平,血浆ADMA水平可作为2型糖尿病动脉粥样硬化发生及发展的预测因子。Aim To investigate the correlation of dimethyl arginine dimethylamine hydrolase 2 （DDAH2） geue -449G/C polymorphism and plasma asymmetric dimethylarginine （ADMA） levels with atherosclerosis in type 2 diabetes （T2DM）. Methods The DDAH2 gene -449G/C polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism （PCR-RFLP） in 146 normal controls and 238 patients with type 2 diabetes （including 80 without atherosclerosis patients （D0 group）, 71 early atherosclerosis patients （D1 group）, 87 middle-late atherosclerosis patients （ D2 group） ）. The plasma levels of ADMA were detected by enzyme linked immunosorbent assay （ELISA）. The genotype frequencies, allele frequencies and clinical index were compared among these groups. Results The G/G genotype frequencies and G allele frequencies in D1 ＋ D2 group were significantly higher than those in DO group （ P 〈 0. 05 ）. In patients with type 2 diabetes, plasma ADMA level in G/G genotype group was significantly higher than that in C/C＋G/C genotype （P〈0.05）. TheADMA levels among groups ： D1 ＋D2 group〉D0 group, 1）2 group〉D1 group〉DO group. A statistically significant difference was revealed after performing covariance analysis on the data （ P 〈 0. 01 ）. Logistic regression ana｜ysis showed that plasma ADMA levels were the determinants of the occurrence and development of atherosclerosis. The G/G genotypes of DDAH2 gene were the determinants in atherosclerosis patients. Conclusions The G/G genotype of DDAI-12 gene may be genetic predisposing factor of atherosclerosis in patients with type 2 diabetes in the Han population of Yunnan. The G/G genotype of DDAH2 gene carries higher ADMA levels. The level of plasma ADMA may be a predictor of the occurrence and development of atherosclerosis in patients with type 2 diabetes.

关 键 词：二甲基精氨酸二甲胺水解酶2 基因多态性 非对称性二甲基精氨酸 2型糖尿病 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]