ACE gene polymorphism and IgA nephropathy: An ethnically homogeneous study and a meta-analysis
ACE gene polymorphism and IgA nephropathy: An ethnically homogeneous study and a meta-analysis
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DOI：
10.1046/j.1523-1755.2001.060002732.x
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发表时间：
2001-08-01
影响因子：
19.6
通讯作者：
Gesualdo, L
中科院分区：
文献类型：
--
作者：
Schena, FP;D'Altri, C;Gesualdo, L
背景。相互矛盾的结果暗示了血管紧张素转换酶（ACE） D等位基因在IgA肾病（IgAN）患者肾损害进展中的作用。这些发现大多是通过异质研究获得的。我们通过聚合酶链反应（PCR）对意大利南部IgAN患者的基因组DNA进行扩增，研究了ACE插入/缺失（I/D）基因多态性。在247例经活检证实的IgAN患者和205名健康受试者中，研究了ACE I/D基因多态性与该病发展的关系。根据肌酐清除率随时间的斜率，对136例随访大于或等于3年的患者和221例随访大于或等于1年的患者进行肾脏损害进展的相关性评估，并通过肾脏生存的单因素和多因素分析进行评估。在Medline数据库中检索的七项研究的荟萃分析中进一步估计了这些关联。采用Mantel-Haenszel-Peto方法进行meta分析，并通过Breslow-Day.Results采用chi(2)检验确定研究的同质性。本研究未发现患者与对照组、肾功能稳定患者与肾功能恶化患者之间ACE I/D基因分布差异。一项针对高加索人和亚洲人的研究分别进行的荟萃分析显示，ACE IID基因多态性与IgAN发生的遗传易感性无关（总OR 0.93, 95% CI）。0.71至1.23：和0.95。95%可信区间。0.64到1.42。分别)或肾脏损害的进展(总or为1.12。95%可信区间。0.67 ~ 1.88；和2.26。95%可信区间。0.75到6.79。（分别）。我们的研究和荟萃分析建议在解释纳入异质人群的关联研究结果时要谨慎。使用新测试的进一步研究。没有由于人口分层和种族造成的偏见。是必要的。
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 homogenous 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 greater than or equal to3 years according to the slope of the creatinine clearance against time, and in 221 patients with a follow-up of greater than or equal to1 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 IID 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.