Kunz R, Bork J P, Fritsche L, Ringel J, Sharma A M
Department of Internal Medicine, Universitätsklinikum Charité, Humboldt University Berlin, Germany.
J Am Soc Nephrol. 1998 Sep;9(9):1653-63. doi: 10.1681/ASN.V991653.
Recent studies have implicated a variant of the angiotensin-converting enzyme gene (ACE), associated with increased activity of this enzyme, in the development and progression of diabetic nephropathy. This study provides a systematic review of all cross-sectional, case-control, and cohort studies in patients with insulin-dependent (IDDM) or non-insulin-dependent (NIDDM) diabetes mellitus of any race, examining the relationship between the ACE-insertion/deletion polymorphism and nephropathy. Nineteen studies in 21 populations published between 1994 and 1997 presenting data on 5336 patients were reviewed. Two investigators independently assessed the studies on methodologic quality, performance of study, and association between the ACE-insertion/deletion polymorphism and nephropathy. Separate analyses of the relationship between genotype and allele frequencies were performed for patients with IDDM and NIDDM by race, using Peto's odds ratio. In Caucasians with IDDM, pooling was not performed due to heterogeneity of the studies, but among the homogeneous studies, no association was detected. Likewise, no association was observed in Caucasian patients with NIDDM (odds ratio [OR], 1.10; 95% confidence interval [95% CI], 0.83 to 1.45). In Asian patients with NIDDM, the risk of nephropathy was increased in the presence of the DD or ID genotype (OR, 1.88; 95% CI, 1.42 to 2.85). Although this analysis fails to confirm an association between the ACE-insertion/deletion genotype and nephropathy in Caucasians with NIDDM or IDDM, a role for this genetic marker in Asian patients cannot be ruled out. However, due to methodologic limitations of individual studies, no definite conclusions can be drawn from this analysis. Clearly, more rigorous methodology needs to be applied in future studies.
近期研究表明，血管紧张素转换酶基因（ACE）的一种变体与该酶活性增加有关，参与了糖尿病肾病的发生和发展。本研究对所有涉及任何种族的胰岛素依赖型（IDDM）或非胰岛素依赖型（NIDDM）糖尿病患者的横断面、病例对照和队列研究进行了系统综述，探讨ACE插入/缺失多态性与肾病之间的关系。对1994年至1997年间发表的21个群体中的19项研究进行了综述，这些研究提供了5336例患者的数据。两名研究者独立评估了这些研究的方法学质量、研究执行情况以及ACE插入/缺失多态性与肾病之间的关联。采用Peto比值比，按种族对IDDM和NIDDM患者的基因型和等位基因频率之间的关系进行了单独分析。在患有IDDM的白种人中，由于研究的异质性未进行合并分析，但在同类研究中未发现关联。同样，在患有NIDDM的白种人患者中也未观察到关联（比值比[OR]为1.10；95%置信区间[95%CI]为0.83至1.45）。在患有NIDDM的亚洲患者中，存在DD或ID基因型时肾病风险增加（OR为1.88；95%CI为1.42至2.85）。虽然该分析未能证实ACE插入/缺失基因型与患有NIDDM或IDDM的白种人肾病之间存在关联，但不能排除该遗传标记在亚洲患者中的作用。然而，由于个别研究的方法学局限性，无法从该分析中得出明确结论。显然，未来的研究需要应用更严格的方法学。
