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TLR4基因的rs5030717和rs5030718变异在2型糖尿病肾病、高血压和血脂异常风险预测中的作用

Role of variants rs5030717 and rs5030718 of TLR4 in the risk prediction of nephropathy, hypertension and dyslipidaemia in type 2 diabetes mellitus.

作者信息

Abbas S A, Raza S T, Mir S S, Siddiqi Z, Zaidi A, Zaidi Z H, Mahdi F

机构信息

a Department of Biochemistry , Era's Lucknow Medical College and Hospital , Lucknow , India.

d Department of Bioengineering , Integral University , Lucknow , India.

出版信息

Br J Biomed Sci. 2018 Oct;75(4):163-168. doi: 10.1080/09674845.2018.1477033. Epub 2018 Sep 13.

Abstract

BACKGROUND

Type 2 diabetes mellitus describes a metabolic disorder characterised by prolonged elevated blood glucose that brings a risk of developing microvascular and macrovascular disease. Several factors, such as dysregulation of the Toll-like receptor 4 (TLR-4), are reputed to contribute to the multiple pathophysiological disturbances responsible for impaired glucose homeostasis. We hypothesised that variants rs5030717 and rs5030718 of TLR4 are associated with diabetic nephropathy, hypertension and dyslipidaemia.

MATERIAL & METHODS: We recruited 370 diabetics (122 with nephropathy, 119 with hypertension and 129 with dyslipidaemia) and 120 ethnicity matched healthy controls. TLR4 polymorphisms were evaluated using polymerase chain reaction followed by restriction fragment length polymorphism analysis. The genotyping data were compared between cases and controls using chi-square test and logistic regression analysis.

RESULTS

Although there was no overall difference in the genotype frequencies of TLR4 rs5030717 in diabetes v controls, the genotype frequencies of diabetic dyslipidaemia cases compared with controls were different (p = 0.001). Overall, the rs5030718 GA and GG genotype frequencies in the entire diabetes cohort were different from those of the controls (p = 0.037), and the frequencies of diabetic nephropathy cases (p = 0.03) and diabetic dyslipidaemia cases were different (p = 0.001) compared with controls. There were no links with diabetic hypertension.

CONCLUSION

TLR4 polymorphisms rs5030717 and rs5030718 may be useful in predicting those type 2 diabetics who are at risk of hypertension, nephropathy and/or dyslipidaemia.

摘要

背景

2型糖尿病是一种代谢紊乱疾病,其特征为血糖长期升高,会带来微血管和大血管疾病的发病风险。多种因素,如Toll样受体4(TLR-4)失调,被认为与导致葡萄糖稳态受损的多种病理生理紊乱有关。我们推测TLR4的rs5030717和rs5030718变体与糖尿病肾病、高血压和血脂异常有关。

材料与方法

我们招募了370名糖尿病患者(122名患有肾病,119名患有高血压,129名患有血脂异常)以及120名种族匹配的健康对照者。使用聚合酶链反应随后进行限制性片段长度多态性分析来评估TLR4基因多态性。使用卡方检验和逻辑回归分析比较病例组和对照组的基因分型数据。

结果

尽管糖尿病患者与对照组相比,TLR4 rs5030717的基因型频率没有总体差异,但糖尿病血脂异常病例与对照组的基因型频率不同(p = 0.001)。总体而言,整个糖尿病队列中rs5030718的GA和GG基因型频率与对照组不同(p = 0.037),糖尿病肾病病例(p = 0.03)和糖尿病血脂异常病例的频率与对照组相比也不同(p = 0.001)。与糖尿病高血压没有关联。

结论

TLR4基因多态性rs5030717和rs5030718可能有助于预测那些有高血压、肾病和/或血脂异常风险的2型糖尿病患者。

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