C332C Genotype of Glyoxalase 1 and its Association with Late Diabetic Complications Glo1 Genotype and Diabetic Neuropathy

C332C Genotype of Glyoxalase 1 and its Association with Late Diabetic Complications Glo1 Genotype and Diabetic Neuropathy
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DOI:
10.1055/s-0033-1345124
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发表时间:
2013-07-01
影响因子:
1.8
通讯作者:
Rudofsky, G.
Rudofsky, G.
中科院分区:
医学4区
文献类型:
--
作者:
Groener, J. B.;Reismann, P.;Rudofsky, G.

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目的/前言:乙二酸酶1催化甲基乙醛的解毒作用,甲乙醛是晚期糖基化终末产物的主要前体,与衰老、神经退行性疾病和糖尿病的微血管并发症有关。在这里,我们研究了乙醛酸酶1基因(Glo1 A332C,rs4746或rs2736654)单核苷酸多态与1型和2型糖尿病微血管并发症发生率的关系。材料和方法:采用聚合酶链式反应和限制性内切酶BSA I酶切方法对209例1型糖尿病患者和524例2型糖尿病患者进行基因分型。结果:乙醛酸酶1基因分型频率在不同糖尿病类型中不同,A332A型在1型糖尿病患者中的患病率显著高于2型糖尿病患者(35.9%vs.27.3%;p=0.03)。在1型糖尿病中,任何基因与糖尿病视网膜病变、肾病或神经病变均无相关性。相比之下,C332C等位基因纯合的2型糖尿病患者糖尿病神经病变的患病率显著增加(P=0.03;OR=1.49[95%-CI:1.04;2.11]),但未发现与糖尿病肾病或视网膜病变相关。结论:乙醛酶1基因C332C-基因型可能与2型糖尿病神经病变有关,支持甲基乙二醛可能是2型糖尿病神经病变的重要介导物的假说。
Aims/Introduction: Glyoxalase 1 catalyses the detoxification of methylglyoxal, a major precursor of advanced glycation end products associated with aging, neurodegenerative diseases, and microvascular complications of diabetes. Here, we examine a possible association of a single nucleotide polymorphism of glyoxalase 1 gene (Glo1 A332C, rs4746 or rs2736654) with the prevalence of microvascular diabetic complications in patients with type 1 and type 2 diabetes.Materials and Methods: Genotyping was performed in 209 patients with type 1 and 524 patients with type 2 diabetes using polymerase chain reaction and subsequent cleavage by restriction endonuclease Bsa I.Results: Frequencies of the glyoxalase 1 genotypes were different with respect to diabetes type with a significantly higher prevalence of A332A-genotype in type 1 diabetes (35.9% vs. 27.3%; p = 0.03). In type 1 diabetes, there was no correlation of any genotype with diabetic retinopathy, nephropathy or neuropathy. In contrast, type 2 diabetic patients homozygous for the C332C allele showed a significantly increased prevalence of diabetic neuropathy (p = 0.03; OR = 1.49 [ 95%-CI: 1.04; 2.11]), while no association with diabetic nephropathy or retinopathy was found. However, the significance of this association was lost after correction for multiple testing.Conclusions: Our data suggest a possible association of C332C-genotype of the glyoxalase 1 gene with diabetic neuropathy in type 2 diabetes, supporting the hypothesis that methylglyoxal might be an important mediator of diabetic neuropathy in type 2 diabetes.