血管紧张素转化酶和载脂蛋白E基因多态性对新诊2型糖尿病患者亚临床动脉粥样硬化的预测
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国家“十五”攻关项目(2001BA702B01,2001BA702B04);湖南省科技厅项目(02SSY3065)


Association of Angiotensin 1 Converting Enzyme and Apolipoprotein E Gene Polymorphisms with the Risk of Subclinical Atherosclerosis in Newly Diagnosed Type 2 Diabetes
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    目的为探讨血管紧张素转化酶和载脂蛋白E基因多态性与新诊2型糖尿病多因素强化干预条件下亚临床动脉粥样硬化发生的关系。方法采用聚合酶链反应—限制性片段长度多态性方法检测湖南地区汉族新诊2型糖尿病患者及93例无糖尿病对照者血管紧张素转化酶及载脂蛋白E的基因多态性,分别比较血管紧张素转化酶和载脂蛋白E基因型间以及两基因型协同作用下体重、血糖、血压、血脂和胰岛素抵抗等代谢指标水平的差异,比较分析无动脉粥样硬化与亚临床动脉粥样硬化患者血管紧张素转化酶及载脂蛋白E基因型分布特点。采用Logistic回归模型分析血管紧张素转化酶、载脂蛋白E基因型及二者协同作用下与多因素干预条件下亚临床动脉粥样硬化发生的关系。结果157例新诊2型糖尿病患者中,载脂蛋白E基因型及等位基因频率分布与对照组比较差异无显著性(p>0.05);血管紧张素转化酶Ⅰ等位基因频率显著高于对照组(0.707比0.581,p<0.05),血管紧张素转化酶DD携带者收缩压水平与II及ID携带者比较差异无显著性(p>0.05)。载脂蛋白E4/X基因型携带者低密度脂蛋白胆固醇水平显著高于2/X携带者(p<0.01);血管紧张素转化酶及载脂蛋白E基因型对收缩压及低密度脂蛋白胆固醇水平无交互作用。两基因多态性与各代谢指标干预1年达标情况和动脉内中膜厚度无相关关系(p>0.05)。血管紧张素转化酶DD携带者无一例发生亚临床动脉粥样硬化,与非DD携带者比较差异接近显著性(P=0.059),未发现载脂蛋白E基因多态性与亚临床动脉粥样硬化发生的相关性。结论以上提示,载脂蛋白E基因多态性对新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化的发生无预测作用;血管紧张素转化酶DD基因型可能是新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化发生的负性预测因子。

    Abstract:

    Aim To investigate the relationship between angiotensin converting enzyme (ACE), apoE gene polymorphisms and the risk of subclinical atherosclerosis (As) in newly diagnosed type 2 diabetes after multifactorial intensified intervention. Methods The DNA polymorphisms in ACE and apoE were determined by PCR-RFLP between 157 newly diagnosed diabetic patients and 93 controls in Han's population of Hunan. Data of body weight, HbA1c, blood pressure, blood lipid and insulin resistance were compared among the groups with different genotypes of ACE and apoE. Characteristics of ACE and apoE gene polymorphisms were compared between patients with and without subclinical As. The association of the risk of subclinical As and apoE, ACE genotypes and their synergistic effects were determined by Logistic regression analysis. Results Frequencies of apoE genotypes in 157 individuals were not different between patients and controls (p>0.05), whereas the frequencies of ACE-I alleles were significantly higher than that in the controls (0.707 vs 0.581, p<0.05). No significant relationship was identified between ACE polymorphisms and blood pressure in this population. ApoE4/X carriers had higher LDLC than that in 2/X carriers (3.19±0.84 mmol/L vs 2.42±0.37 mmol/L, p<0.01). No synergistic effect was found in ACE and apoE geno-type on sBP or LDLC level. There was no association between targeted value of metabolic parameters, arterial intima-medial thickness and the two gene polymorphisms. Meanwhile, no correlation was found between apoE genotypes and the incidence of subclinical As. None of the patients with ACE-DD homozygote suffered from subclinical As, approaching significant difference compared to patients with ACE -II and ID genotype(P=0.059). Conclusions ApoE gene polymorphism may benotapre-dictor, but ACE-DD genotype might be a negative one for the development of subclinical As in patients with newly diagnosed type 2 diabetes after one-year multifactorial intervention.

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陈小燕,周智广,唐炜立,周启昌,颜湘,彭健,刘志文.血管紧张素转化酶和载脂蛋白E基因多态性对新诊2型糖尿病患者亚临床动脉粥样硬化的预测[J].中国动脉硬化杂志,2005,13(3):340~344.

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  • 收稿日期:2004-04-26
  • 最后修改日期:2004-11-05
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