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肾素-血管紧张素系统基因多态性与2型糖尿病肾病的相关性

[Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes].

作者信息

Buraczyńska Monika, Ksiazek Piotr, Łopatyński Jerzy, Spasiewicz Danuta, Nowicka Teresa, Ksiazek Andrzej

机构信息

Katedra i Klinika Nefrologii AM w Lublinie.

出版信息

Pol Arch Med Wewn. 2002 Aug;108(2):725-30.

PMID:12476891
Abstract

Diabetic nephropathy is the most frequent cause of end-stage renal failure. One of the crucial factors in a development of renal and cardiovascular complications of diabetes is genetic predisposition. The genes of the renin-angiotensin system are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was the evaluation of a possible role of genetic polymorphisms of some of the RAS system genes in the nephropathy in type 2 diabetes. The study was performed in 117 patients with diabetic nephropathy, compared with 200 healthy subjects as a control group. The following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme gene (ACE), M235T of the angiotensinogen gene (AGT) and A1166C of the angiotensin II type 1 receptor gene (AT1R) were evaluated by polymerase chain reaction (PCR). No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. The results for the AT1R gene polymorphism revealed significant differences in allele and genotype frequencies. The homozygous CC genotype was more frequent in patients with diabetic nephropathy than in control group. Both genotypes with the C allele (AC + CC) were found in 56% of patients compared to 38% in control group. These results suggest increased susceptibility to diabetic nephropathy in individuals carrying the CC genotype. Therefore, the A1166C polymorphism of the AT1R gene could be a potential genetic marker for increased susceptibility to renal complications in type 2 diabetes.

摘要

糖尿病肾病是终末期肾衰竭最常见的病因。糖尿病肾脏和心血管并发症发生发展的关键因素之一是遗传易感性。肾素-血管紧张素系统基因是参与慢性肾脏疾病发病机制的重要候选基因群体。我们研究的目的是评估肾素-血管紧张素系统(RAS)某些基因的基因多态性在2型糖尿病肾病中可能发挥的作用。该研究纳入了117例糖尿病肾病患者,并与200名健康受试者作为对照组进行比较。通过聚合酶链反应(PCR)评估了以下多态性:血管紧张素转换酶基因(ACE)的插入/缺失(I/D)、血管紧张素原基因(AGT)的M235T以及血管紧张素II 1型受体基因(AT1R)的A1166C。在ACE和AGT多态性的等位基因频率和基因型分布方面,两组之间未发现统计学上的显著差异。AT1R基因多态性的结果显示等位基因和基因型频率存在显著差异。糖尿病肾病患者中纯合CC基因型比对照组更常见。携带C等位基因的两种基因型(AC + CC)在56%的患者中出现,而对照组为38%。这些结果表明,携带CC基因型的个体患糖尿病肾病的易感性增加。因此,AT1R基因的A1166C多态性可能是2型糖尿病肾脏并发症易感性增加的潜在遗传标志物。

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[Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes].肾素-血管紧张素系统基因多态性与2型糖尿病肾病的相关性
Pol Arch Med Wewn. 2002 Aug;108(2):725-30.
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ACE variants interact with the RAS pathway to confer risk and protection against type 2 diabetic nephropathy.ACE 变体与 RAS 通路相互作用,导致 2 型糖尿病肾病的发病风险和保护作用。
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引用本文的文献

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Angiotensinogen Gene Missense Polymorphisms (rs699 and rs4762): The Association of End-Stage Renal Failure Risk with Type 2 Diabetes and Hypertension in Egyptians.血管紧张素原基因错义多态性(rs699 和 rs4762):埃及人终末期肾衰竭风险与 2 型糖尿病和高血压的相关性。
Genes (Basel). 2021 Feb 25;12(3):339. doi: 10.3390/genes12030339.
2
Angiotensinogen (AGT) gene missense polymorphisms (rs699 and rs4762) and diabetic nephropathy in Caucasians with type 2 diabetes mellitus.血管紧张素原(AGT)基因错义多态性(rs699 和 rs4762)与 2 型糖尿病高加索人群的糖尿病肾病。
Bosn J Basic Med Sci. 2017 Aug 20;17(3):262-267. doi: 10.17305/bjbms.2017.1823.
3
Association between two genetic polymorphisms of the renin-angiotensin-aldosterone system and diabetic nephropathy: a meta-analysis.
肾素-血管紧张素-醛固酮系统的两个遗传多态性与糖尿病肾病的关系:一项荟萃分析。
Mol Biol Rep. 2012 Feb;39(2):1293-303. doi: 10.1007/s11033-011-0862-7. Epub 2011 May 20.
4
Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus.2型糖尿病患者血管紧张素2 1型受体和血管紧张素原的基因多态性与肾功能不全及冠心病风险
BMC Nephrol. 2009 Mar 27;10:9. doi: 10.1186/1471-2369-10-9.
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Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies.血管紧张素转换酶插入/缺失多态性与糖尿病和非糖尿病肾病中的肾脏保护作用
Clin J Am Soc Nephrol. 2008 Sep;3(5):1511-25. doi: 10.2215/CJN.04140907. Epub 2008 Jun 11.