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沙特阿拉伯卡西姆地区内皮型一氧化氮合酶基因G894T多态性与糖尿病肾病风险的关联——一项初步研究

Association of the endothelial nitric oxide synthase gene G894T polymorphism with the risk of diabetic nephropathy in Qassim region, Saudi Arabia-A pilot study.

作者信息

Mackawy Amal Mohammed Husein, Khan Amjad Ali, Badawy Mohammed El-Sayed

机构信息

Medical Biochemistry and Molecular Biology, Faculty of MEdicine, Zagazig University and Medical Laboratory department, Applied Medical Science, Qassim University, Saudi Arabia.

Applied Medical Science College, Qassim University, Saudi Arabia.

出版信息

Meta Gene. 2014 May 21;2:392-402. doi: 10.1016/j.mgene.2014.04.009. eCollection 2014 Dec.

Abstract

BACKGROUND

Diabetic nephropathy (DN) is a chronic microangiopathic complication of type 2 diabetes mellitus (DM).Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the vascular endothelial cells has been suggested as playing an important role in the pathogenesis of diabetic nephropathy (DN). Endothelial nitric oxide synthase (E-NOS) gene G894T polymorphism has been reported to be associated with endothelial dysfunction leading to DN. Our objective was to evaluate the association of G894T polymorphism of eNOS gene with the risk of DN among type 2 diabetic Saudi patients.

METHODS

One hundred and twenty subjects were included in this study. They were divided into three groups. Group I, 40 controls. Group II, 40 type 2 diabetic patients without nephropathy. Group III, 40 type2 diabetic patients with nephropathy. Endothelial nitric oxide synthase (eNOS) G894Tpolymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma nitric oxide (NO) levels were estimated.

RESULTS

E-NOS genotype frequency showed non-significant differences among the all studied groups (p > 0.05). Both diabetic groups had significantly higher plasma nitrate levels than in controls with a significant increase in group III than in group II patients (all p < 0.0001). E NOS 894TT genotype was associated with higher plasma nitrate levels in all groups.

CONCLUSION

E-NOS gene SNP is not considered as genetic risk factor for DN among type 2 diabetic Saudi patients. The higher plasma levels of nitrates as a marker of oxidative stress in diabetic patients with nephropathy suggest the possible role of oxidative stress but not e-NOS gene SNP in pathogenesis of the DN.

摘要

背景

糖尿病肾病(DN)是2型糖尿病(DM)的一种慢性微血管并发症。血管内皮细胞中一氧化氮合酶(NOS)活性受损导致的血管内皮功能障碍被认为在糖尿病肾病(DN)的发病机制中起重要作用。据报道,内皮型一氧化氮合酶(E-NOS)基因G894T多态性与导致DN的内皮功能障碍有关。我们的目的是评估2型糖尿病沙特患者中eNOS基因G894T多态性与DN风险的相关性。

方法

本研究纳入120名受试者。他们被分为三组。第一组,40名对照组。第二组,40名无肾病的2型糖尿病患者。第三组,40名患有肾病的2型糖尿病患者。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测内皮型一氧化氮合酶(eNOS)G894T多态性。估计血浆一氧化氮(NO)水平。

结果

E-NOS基因型频率在所有研究组之间无显著差异(p>0.05)。两个糖尿病组的血浆硝酸盐水平均显著高于对照组,第三组患者的血浆硝酸盐水平显著高于第二组患者(所有p<0.0001)。E NOS 894TT基因型与所有组中较高的血浆硝酸盐水平相关。

结论

在2型糖尿病沙特患者中,E-NOS基因单核苷酸多态性不被认为是DN的遗传危险因素。在患有肾病的糖尿病患者中,较高的血浆硝酸盐水平作为氧化应激的标志物,提示氧化应激可能起作用,但不是e-NOS基因单核苷酸多态性在DN发病机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9571/4287856/31e461999b02/gr1.jpg

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