血管紧张素转换酶（ACE）基因插入/缺失多态性对中国2型糖尿病患者肾脏及心血管临床结局的预后影响

Prognostic effect of insertion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes.

作者信息

Wang Ying, Ng Maggie C Y, So Wing Yee, Tong Peter C Y, Ma Ronald C W, Chow Chun Chung, Cockram Clive S, Chan Juliana C N

机构信息

Department of Medicine & Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

出版信息

Diabetes Care. 2005 Feb;28(2):348-54. doi: 10.2337/diacare.28.2.348.

DOI:10.2337/diacare.28.2.348

PMID:15677791

Abstract

OBJECTIVE

The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 +/- 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine >/=500 micromol/l, or doubling of plasma creatinine of baseline value >/=150 micromol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis.

RESULTS

The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49-5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points.

CONCLUSIONS

The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 diabetes.

摘要

目的

据报道，血管紧张素转换酶（ACE）基因的插入/缺失（I/D）多态性与糖尿病微血管或大血管并发症相关。本研究旨在探讨I/D多态性对中国2型糖尿病患者肾脏和心血管临床结局的预后影响。

研究设计与方法

对1281例中国2型糖尿病患者进行连续队列研究，随访时间为41.3±21.6个月。肾脏终点定义为肾脏死亡和事件（需要透析、血浆肌酐≥500微摩尔/升，或血浆肌酐较基线值翻倍且≥150微摩尔/升）。心血管终点定义为心血管死亡和事件，包括缺血性心脏病、心力衰竭、脑血管意外以及需要住院治疗的血运重建。采用聚合酶链反应（PCR）及琼脂糖凝胶电泳检测ACE基因的I/D多态性。

结果

ACE基因I/D多态性频率符合哈迪-温伯格平衡。发生肾脏终点事件的患者（n = 98）与未发生的患者（n = 1183）相比，DD基因型频率更高（19.4%对10.8%，P = 0.018），D等位基因频率更高（41.3%对31.8%，P = 0.006）。II基因型携带者（n = 595）、DI基因型携带者（n = 539）和DD基因型携带者（n = 147）的肾脏终点累积发生率分别为10.0%、19.2%和24.4%（对数秩检验P = 0.004）。在多因素Cox回归分析中，I/D多态性对肾脏终点事件的发生仍有显著影响，DD基因型具有明显的有害作用（DD与II相比，调整后风险比为2.80 [95%可信区间1.49 - 5.29]）。I/D多态性对心血管终点事件无预后影响。