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
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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


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

    Abstract:

    Aim To investigate the correlation of dimethyl arginine dimethylamine hydrolase 2(DDAH2) gene -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 D0 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). The ADMA levels among groups: D1+D2 group>D0 group,D2 group>D1 group>D0 group. A statistically significant difference was revealed after performing covariance analysis on the data (P<0.01).Logistic regression analysis 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 DDAH2 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.

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石 柔,杨晶晶,刘 华,陈洪艳,雷又鸣,宋滇平. 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[J].中国动脉硬化杂志,2015,23(09):896~901.

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  • 收稿日期:2014-11-19
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  • 在线发布日期: 2015-07-21