Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients - interaction with ACE insertion/deletion polymorphism
Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients - interaction with ACE insertion/deletion polymorphism
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DOI：
10.1038/sj.ki.5000097
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发表时间：
2006-04-01
影响因子：
19.6
通讯作者：
Chan, JCN
中科院分区：
文献类型：
--
作者：
So, WY;Ma, RCW;Chan, JCN
血管紧张素转换酶（ACE）插入（I）/缺失（D）多态性可能改变抑制肾素-血管紧张素-醛固酮系统（RAAS）对2型糖尿病患者生存率和心肾结局的影响。采用聚合酶链反应方法对2089例中国2型糖尿病患者（平均（+/-标准差）年龄为59.7 +/- 13.1岁）进行该多态性基因分型，并前瞻性随访中位时间为44.6（四分位距：23.7，57.5）个月。临床结果，包括全因死亡率，心血管和肾脏终点，进行了检查。I等位基因频率为67.1%，D等位基因频率为32.9%，3、DI和DD的基因型频率分别为45.8%、42.6%和11.6%。ACE DD多态性是肾脏终点的独立预测因子，风险比（HR）为1.72（1.16，2.56），但不是心血管终点或死亡率的独立预测因子。在控制包括ACE I/D基因型在内的混杂因素后，RAAS抑制剂的使用与死亡率（HR 0.34（0.23，0.50））和肾脏终点（HR 0.55（0.40，0.75））风险降低相关。在亚组分析中，（II vs DI vs DD：HR 0.29（0.16，0.51）vs 0.25（0.14，0.46）vs 1.33（0.41，4.31））和肾保护（II vs DI vs DD：0.52（0.30，0.90）vs 0.43（0.25，0.72）vs 0.95（0.43，2.12））在II和DI携带者中最明显。总之，在中国2型糖尿病患者中，抑制RAAS与降低死亡率和肾脏终点发生风险相关。这些好处在II和DI携带者中最为明显。
Angiotensin-converting enzyme (ACE) insertion( I)/deletion ( D) polymorphism may modify the effect of inhibition of the renin - angiotensin - aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 ( interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality ( HR 0.34 (0.23, 0.50)) and renal end point ( HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection ( II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 ( 0.25, 0.72) vs 0.95 ( 0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.