ACE、PAI-1基因多态性对新诊断T2DM患者颈动脉内中膜厚度进展的预测作用  

The predicting effects of ACE gene and PAI-1 gene polymorphisms on CCA-IMT progression in newly diagnosed T2DM

作　　者：刘玉华[1] 周智广[2] 谭少珍[2] 林健[2] 唐炜立[2] 刘志文[2] 何霞[2] 熊斌[2] 

机构地区：[1]广东省东莞市人民医院综合科,广东东莞523018 [2]中南大学湘雅二医院代谢内分泌研究所中南大学糖尿病中心

出　　处：《中国医师杂志》2009年第7期868-870,874,共4页Journal of Chinese Physician

基　　金：国家十五科技攻关资助项目（2001BA702B01,2001BA702B04）,湖南省科技厅资助项目（02SSY3065）

摘　　要：目的探讨多危因素强化干预条件下，血管紧张素转换酶（ACE）、纤溶酶原激活物抑制物-1（PAI-1）基因多态性对新诊T2DM患者颈总动脉内中膜厚度（CCA-IMT）的预测作用。方法检测308例T2DM及93例健康对照ACE及PAI-1基因型及CCA—IMT，并对170例病程1年以内、无亚临床AS的T2DM进行干预治疗，探讨ACE及PAI-1基因型与CCA—IMT进展的关系。结果携带ACEDD基因型者CCA—IMT高于携带II及ID基因型者（P〈0．05）；同时携带ACEDD及PAI-1 4CAG基因型者CCA-IMT显著高于其他任何基因型及其组合者（P〈0．01）。强化干预后，CCA-IMT非进展组PAI-1 4G等位基因、4G4G基因型携带者比例高于进展组（P〈0．05）。结论ACE DD基因型与PAI-1 4GdG基因型协同作用是T2DM患者CCA-IMT增加的独立危险因素。多危险因素强化干预条件下PAI-1 4G／4G基因型可能是新诊T2DM患者CCA-IMT进展的负性预测因子。Objective The study was to investigate the relationship among angiotensin 1-converting enzyme （ACE）, plasminogen activator inhibitor-1 （ PAI-1 ） gene polymorphisms and the common carotid artery （ CCA-IMT）, and the predicting effects of them on CCA-IMT in newly diagnosed type 2 diabetes （T2DM）. Methods The polymorphisms of ACE （I/D） gene and PAI-1 （4G/5G） gene were determined by polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP） and allele-specific polymerase chain reaction （AS-PCR） method in 308 cases with T2DM. CCA-IMT was compared among the groups with different genotypes of ACE and PAI-1. The in- dependent or synergistic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on CCA-IMT in 308 patients with T2DM were analyzed with multivariate linear regression. Then the 156 newly diagnosed type 2 diabetics （durations〈 1 year） without AS received the muhifactorial targeted intervention, including taking aspirin and controlling blood glucose, blood pressure, blood lipid and body weight. The differences of metabolic control, ACE （I/D） and PAI-1 （4G/5G） gene polymorphisms were analyzed. Logistic regression analysis was used to analyze the correlation among the CCA-IMT, ACE （I/D） and PAI-1 （4G/5G） polymorphisws. Results Patients with ACE DD genotypes had higher CCA-IMT than those with ACE-II or ACE ID genotypes. Patients with both ACE DD and PAI-1 4G4G genotypes had a higher CCA-IMT than those with any other pairs of genotypes. Multivariate linear regression analysis showed that ACE DD and PAI-1 4G4G gene polymorphisms had synergistic effect on the CCA-IMT in T2DM patients. After 2 years muhifactorial intervention, the frequencies of PAI-1 4G alleles and 4G4G genotypes were lower than those in the CCA-IMT non-increasing group. Conclusions These findings indicate that the ACE-DD genotype and its synergistic effects with the PAI-1 4G/4G genotype are independent risk factors for the CCA-IMT in T2DM patients. Under multi- factorial interven

关 键 词：肽基二肽酶A/遗传学 纤溶酶原激活物抑制物1/遗传学 多态现象 遗传 糖尿病 2型/病理学 血管中膜 

分 类 号：R54[医药卫生—心血管疾病] R587[医药卫生—内科学]