Pereira Tiago Veiga, Nunes Ane Cláudia Fernandes, Rudnicki Martina, Magistroni Ricardo, Albertazzi Alberto, Pereira Alexandre Costa, Krieger José Eduardo
Department of Biochemistry and Molecular Biology, Federal University of São Paulo, Brazil.
Nephrol Dial Transplant. 2006 Nov;21(11):3155-63. doi: 10.1093/ndt/gfl412. Epub 2006 Aug 25.
Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease characterized by an important variability in clinical course, which cannot be fully explained by the genetic heterogeneity of the disease. Although the role for the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a modifier factor in ADPKD renal deterioration has been suggested, direct evidence from genetic association studies remain inconclusive. To provide a more robust estimate of the putative effect of the ACE I/D polymorphism on the renal progression in ADPKD, we performed a meta-analysis pooling data from all relevant studies in which the role of the ACE I/D variant in ADPKD clinical features was evaluated.
We applied a random-effects model to combine odds ratio and 95% confidence intervals. Q-statistic was used to evaluate the homogeneity, and both Egger's and Begg-Mazumdar tests were used to assess publication bias.
Altogether, three distinct meta-analyses were generated using data from 13 studies. Despite the absence of publication bias and the presence of homogeneity among study results, the DD genotype failed to show an influence on risk of end-stage renal disease (ESRD), mean age at ESRD or risk of hypertension in ADPKD patients when compared with I-allele carriers (DD vs ID+II). Likewise, meta-analyses carried out separately for Caucasian and Asian studies showed no indication of an association between the DD genotype and a faster renal deterioration in ADPKD.
These findings do not support the hypothesis that the enhanced ACE activity associated with the D allele might promote a significantly worse prognosis in patients with ADPKD.
常染色体显性多囊肾病（ADPKD）是一种临床病程具有显著变异性的肾脏疾病，而这种变异性无法完全由该疾病的基因异质性来解释。尽管有研究提示血管紧张素I转换酶（ACE）插入/缺失（I/D）多态性作为ADPKD肾脏恶化的修饰因子发挥作用，但基因关联研究的直接证据仍不确凿。为了更可靠地评估ACE I/D多态性对ADPKD肾脏进展的假定影响，我们进行了一项荟萃分析，汇总了所有评估ACE I/D变异在ADPKD临床特征中作用的相关研究数据。
我们应用随机效应模型合并比值比和95%置信区间。采用Q统计量评估同质性，并用Egger检验和Begg-Mazumdar检验评估发表偏倚。
总共利用13项研究的数据进行了三项不同的荟萃分析。尽管不存在发表偏倚且研究结果具有同质性，但与I等位基因携带者（DD与ID+II相比）相比，DD基因型对ADPKD患者的终末期肾病（ESRD）风险、ESRD时的平均年龄或高血压风险均未显示出影响。同样，分别针对白种人和亚洲人群研究进行的荟萃分析也未表明DD基因型与ADPKD中更快的肾脏恶化之间存在关联。
这些发现不支持以下假设，即与D等位基因相关的ACE活性增强可能会使ADPKD患者的预后显著变差。
