Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus
Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus
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DOI：
10.1046/j.0742-3071.2001.00598.x
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发表时间：
2001-11-01
影响因子：
3.5
通讯作者：
Cox, A
中科院分区：
文献类型：
--
作者：
Neamat-Allah, M;Feeney, SA;Cox, A
目的探讨醛糖还原酶基因多态性与1型和2型糖尿病肾病的关系，并对已发表的结果进行荟萃分析。方法：我们研究了两种醛糖还原酶多态性在4个独立队列中的作用，这些队列分别为病例和对照（1型和2型糖尿病各2例），来自两个民族的人群，包括471例肾病患者和494例无肾病的对照糖尿病患者。在每个队列的肾病患者和非肾病对照组中，在醛糖还原酶基因起始位点2.1 kb的位置有一个C/T转换和一个（CA）(n)微卫星标记。结果在4个研究组中，3个研究组携带-106 T等位基因与糖尿病肾病显著相关。Mantel-Haenszel合并优势比为2.22 (95% Cl 1.69, 2.94), P = 1.05 × 10（-8）。我们没有发现微卫星标记物与肾病相关的证据，尽管这两个标记物之间存在中等程度的不平衡。对已发表数据的荟萃分析显示，微卫星标志物与2型糖尿病肾病没有关联，但与1型糖尿病肾病有不同程度的关联。荟萃分析为ALR2-106标志物在糖尿病肾病（DN）中的作用提供了比微卫星标志物更有说服力的证据。现在需要更多的研究来证实这些结果，并确定ALR2-106多态性是否在DN中具有功能作用。
Aims To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results.Methods We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position -106, and a (CA)(n) microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non-nephropathic controls from each cohort.Results Carriage of the -106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel-Haenszel combined odds ratio was 2.22 (95% Cl 1.69, 2.94), P = 1.05 x 10(-8). We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta-analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes.Conclusions Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN.