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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Functional differences between the susceptibility Z-2/C-106 and protective Z + 2/T-106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications
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Functional differences between the susceptibility Z-2/C-106 and protective Z + 2/T-106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications

机译：醛糖还原酶基因的易感性Z-2 / C-106和保护性Z + 2 / T-106启动子区域多态性之间的功能差异可能与糖尿病微血管并发症有关

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摘要

Studies have shown that polymorphisms located at positions -106 and approximately -2100 base pairs (5' ALR2) in the regulatory region of the aldose reductase gene are associated with susceptibility to microvascular complications in patients with diabetes. The aim was to investigate the functional roles of these susceptibility alleles using an in vitro gene reporter assay. Susceptibility, neutral and protective 5'ALR2/-106 alleles were transfected into HepG2 cells and exposed to excess d-glucose (d-glucose at final concentrations 14 or 28 mmol/l). Transcriptional activities were determined using a dual luciferase reporter gene assay. The "susceptibility alleles" Z-2 with C-106 had the highest transcriptional activity when compared with the "protective" combination of Z + 2 with C - 106 alleles (58.7 ± 9.9 vs. 10.1 ± 0.7; P < 0.0001). Those constructs with either the Z or Z-2 in combination with the C-106 allele had significantly higher transcriptional activities when compared to those with the T-106 allele (Z/C-106, 37.4 ± 5.4 vs. Z/T-106 7.7 ± 1.6, P < 0.003; Z - 2/C -106, 58.7 ± 9.9 vs. Z - 2/T - 106 10.9 ± 0.6, P < 0.0001). These results demonstrate that the Z - 2/C - 106 haplotype is associated with elevated transcriptional activity of the aldose reductase gene. This in turn may explain the role of these polymorphisms in the susceptibility to diabetic microvascular complications.
机译：研究表明，醛糖还原酶基因调节区域中-106位和大约-2100个碱基对（5'ALR2）的多态性与糖尿病患者对微血管并发症的敏感性有关。目的是使用体外基因报告基因分析法研究这些易感性等位基因的功能作用。将易感性，中性和保护性5'ALR2 / -106等位基因转染到HepG2细胞中，并暴露于过量的d-葡萄糖（d-葡萄糖的终浓度为14或28 mmol / l）。使用双重萤光素酶报告基因测定测定转录活性。与Z + 2与C-106等位基因的“保护性”组合相比，具有C-106的“易感等位基因” Z-2具有最高的转录活性（58.7±9.9对10.1±0.7; P <0.0001）。与T-106等位基因相比，那些Z或Z-2与C-106等位基因结合的构建体具有更高的转录活性（Z / C-106，37.4±5.4 vs. Z / T-106 7.7±1.6，P <0.003; Z-2 / C -106，58.7±9.9与Z-2 / T-106 10.9±0.6，P <0.0001）。这些结果表明，Z-2 / C-106单倍型与醛糖还原酶基因的转录活性升高有关。这反过来可以解释这些多态性在糖尿病微血管并发症易感性中的作用。

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