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首页> 外文期刊>International Journal of Molecular Epidemiology and Genetics >Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes
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Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes

机译:噻嗪类利尿剂或他汀类药物使用者与2型糖尿病相关的基因表达

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摘要

Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, emQ-value=0.0257/em), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, emQ-value=0.0584/em), CXORF21 (up-regulated 11%, emQ-value=0.0584/em), and ZNHIT3 (up-regulated 19%, emQ-value=0.0959/em), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.
机译:噻嗪类利尿剂和他汀类药物可用于改善心血管疾病的预后,但也可能导致2型糖尿病(T2DM),尽管其机制尚不清楚。基因表达研究可以促进对这些关联的理解。对正在进行的基于人群的研究的参与者进行了抽样,以进行这些外周血微阵列基因表达的纵向研究,然后进行糖尿病的研究。所有样本受试者均为他汀类或噻嗪类使用者。随访期间患糖尿病的患者包括病例(44例噻嗪类药物使用者; 19例他汀类药物使用者),并与因多种因素未患上糖尿病的药物滥用对照组相匹配。在标准化的监督下,替代变量分析消除了技术偏见和混淆。差异表达的基因是那些具有错误发现率Q值& 0.05的基因。与对照组相比,在使用噻嗪类药物的人群中,糖尿病患者的CCL14表达差异显着(下调6%, Q值= 0.0257 )。在他汀类药物使用者中,糖尿病患者的ZNF532(上调15%, Q值= 0.0584 ),CXORF21(上调11%, Q值= 0.0584 )和ZNHIT3(上调19%, Q-value = 0.0959 )。这些基因构成了与药物相关的糖尿病发展的未来表达或机制研究的潜在靶标。

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