血管紧张素转换酶基因多态性与IgA肾病：一项种族同质研究及荟萃分析。

ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis.

作者信息

Schena F P, D'Altri C, Cerullo G, Manno C, Gesualdo L

机构信息

Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Policlinic, Bari, Italy.

出版信息

Kidney Int. 2001 Aug;60(2):732-40. doi: 10.1046/j.1523-1755.2001.060002732.x.

DOI:10.1046/j.1523-1755.2001.060002732.x

PMID:11473656

Abstract

BACKGROUND

Conflicting results have implicated the angiotensin-converting enzyme (ACE) D allele in the progression of renal damage in patients with IgA nephropathy (IgAN). Most of these findings have been obtained by heterogeneous studies.

METHODS

We investigated the ACE insertion/deletion (I/D) gene polymorphism by polymerase chain reaction (PCR) amplification of genomic DNA in an ethnically homogeneous sample size of IgAN patients from Southern Italy. The association between ACE I/D gene polymorphism and the development of the disease was examined in 247 biopsy-proven IgAN patients and 205 healthy subjects. The association with the progression of renal damage was evaluated in 136 patients with a follow-up of > or =3 years according to the slope of the creatinine clearance against time, and in 221 patients with a follow-up of > or =1 year assessing by univariate and multivariate analyses of renal survival. These associations were further estimated in a meta-analysis of seven studies retrieved in the Medline database. The meta-analysis was performed according to the Mantel-Haenszel-Peto method when homogeneity of the studies was established using the chi(2) test by Breslow-Day.

RESULTS

No difference in the ACE I/D gene distribution between patients and controls and between patients with stable and those with deteriorating renal function was found in our study. A meta-analysis performed separately for Caucasian and Asian studies showed that the ACE I/D gene polymorphism did not contribute to the genetic susceptibility of the development of IgAN (total OR 0.93, 95% CI, 0.71 to 1.23; and 0.95, 95% CI, 0.64 to 1.42, respectively) or the progression of the renal damage (total OR 1.12, 95% CI, 0.67 to 1.88; and 2.26, 95% CI, 0.75 to 6.79, respectively) in both groups.

CONCLUSIONS

Our study and meta-analysis suggest caution in the interpretation of results from association studies enrolling heterogeneous populations. Further studies using new tests, which are free of the bias due to population stratification and ethnicity, are warranted.

摘要

背景

相互矛盾的结果表明血管紧张素转换酶（ACE）D等位基因与IgA肾病（IgAN）患者的肾损伤进展有关。这些发现大多来自异质性研究。

方法

我们通过聚合酶链反应（PCR）扩增基因组DNA，对来自意大利南部的种族同质的IgAN患者样本进行了ACE插入/缺失（I/D）基因多态性研究。在247例经活检证实的IgAN患者和205例健康受试者中，检测了ACE I/D基因多态性与疾病发生之间的关联。根据肌酐清除率随时间的斜率，对136例随访时间≥3年的患者以及221例随访时间≥1年的患者进行单因素和多因素肾脏生存分析，评估了其与肾损伤进展的关联。在对Medline数据库中检索到的7项研究进行的荟萃分析中，进一步估计了这些关联。当使用Breslow-Day的chi(2)检验确定研究的同质性时，根据Mantel-Haenszel-Peto方法进行荟萃分析。

结果

在我们的研究中，患者与对照组之间以及肾功能稳定和恶化的患者之间，ACE I/D基因分布没有差异。对高加索人和亚洲人研究分别进行的荟萃分析表明，ACE I/D基因多态性对两组中IgAN发生的遗传易感性（总OR 0.93，95% CI，0.71至1.23；以及0.95，95% CI，0.64至1.42）或肾损伤进展（总OR 1.12，95% CI，0.67至1.88；以及2.26，95% CI，0.75至6.79）均无贡献。