二甲基精氨酸二甲胺水解酶2基因-449G/C多态性及二甲基精氨酸水平与2型糖尿病的相关性研究

Correlation between DDAH2-449G/C polymorphism and plasma ADMA levels in type 2 diabetes

目的研究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T2DM的关系。方法选取T2DM患者（T2DM组）288例和健康对照者（NC组）279名,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测DDAH2基因-449G/C多态性,应用ELISA检测血浆ADMA的浓度。结果（1）T2DM组DDAH2基因-449G/C位点的G/G基因型和G等位基因频率高于NC组（χ^2=16.742、12.178,P〈0.001）;（2）T2DM组DDAH2基因449G/G多态性携带者具有较高的ADMA水平[（11.15±2.71）vs（7.04±1.46）μmol/L,P〈0.05];DDAH2基因-449G/C多态性与胰岛素抵抗指数（HOMA-IR）无相关性（P〉0.05）。（3）T2DM组血浆ADMA水平高于NC组[（9.51±2.44）vs（4.64±0.92）μmmol/L,P〈0.05];（4）ADMA水平与TC、LDL-C、FPG、2 hPG、SBP、DBP呈正相关（P〈0.05）,与HOMA-IR无相关性（P〉0.05）;多元逐步回归分析显示,FPG是血浆ADMA水平的影响因素（P〈0.001）;（5）Logistic回归分析显示,DDAH2-449G/G多态性、血浆ADMA水平是T2DM发生的独立危险因素（P〈0.05）。结论（1）在云南地区汉族人群中,DDAH2基因-449G/G多态性可能是T2DM的遗传危险因素;此基因型携带者具有较高的ADMA水平;（2）T2DM患者血浆ADMA水平升高,FPG是其影响因素;（3）DDAH2基因-449G/C多态性及血浆ADMA水平与HOMA-IR无相关性。

Objective To investigate the correlation between DDAH2 gene — 449G/C polymorphism and plasma ADMA levels in patients with type 2 diabetes（T2DM）.Methods The polymerase chain reaction-restricted fragment length polymorphism（PCR-RFLP） was used to detect DDAH2 gene- 449G/C polymorphism in 288 T2DM（T2DM group） and 279 normal controls（NC group）.The enzyme linked immuno sorbent assay（ELISA） was used to detect plasma levels of ADMA.Results（1） The frequency of G/G genotype and allele G of DDAH2 gene were higher in T2 DM group than that in NC group（χ^2 = 16.742,12.178,P〈0.001）.（2） In T2 DM group,there was higher ADMA levels in G/G genotype carriers[（11.15±2.71） vs（7.04±1.46） μmol/L,P〈0.05].There was no correlation between DDAH2 gene-449G/C polymorphism and HOMA-IR（P〈0.05）.（3）The plasma ADMA levels were higher in T2 DM group than in NC graup[（9.51±2.44） vs（4.64±0.92） μmmol/L,P〈0.05].（4）There were positive correlations between plasma ADMA and TC,LDL-C,FPG,2 hPG,SBP and DBP（P〈0.05）.There was no correlation between plasma ADMA and HOMA-IR（P〈0.05）.Multiple stepwise regression analysis showed that there was a remarkable correlation between plasma ADMA and FPG.（5） Logistic regression analysis showed that DDAH2 — 449G/G genotype and plasma ADMA levels were independent influencing factors of T2DM（P〈0.05）.Conclusion（1） The DDAH2-449G/G genotype with higher ADMA level may be the genetic risk factor of T2 DM in Han population of Yunnan.（2） The plasma ADMA levels increase in T2 DM and markedly associate with FPG.（3）There is no correlation between DDAH2 gene-449G/C polymorphism or plasma ADMA and HOMA-IR.