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埃及患者中MIR-499a表达及种子区域变体(rs3746444)与心血管疾病的关联

Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients.

作者信息

Fawzy Manal S, Toraih Eman A, Hamed Elham O, Hussein Mohammad H, Ismail Hussein M

机构信息

a Department of Medical Biochemistry, Faculty of Medicine , Suez Canal University , Ismailia , Egypt.

b Department of Biochemistry , Faculty of Medicine, Northern Border University , Saudi Arabia.

出版信息

Acta Cardiol. 2018 Apr;73(2):131-140. doi: 10.1080/00015385.2017.1351243. Epub 2017 Aug 8.

DOI:10.1080/00015385.2017.1351243
PMID:28786773
Abstract

BACKGROUND

Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population.

METHODS

Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay.

RESULTS

Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile.

CONCLUSIONS

Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.

摘要

背景

循环微RNA可能是急性心肌梗死(MI)的有力标志物,其功能性基因变异可能增加心血管疾病(CVD)的易感性。本研究旨在量化MI患者血清中微RNA(miR)-499a水平,并与高血压患者和健康受试者进行比较,同时在埃及人群样本中研究其A/G变异rs3746444与CVD的关联。

方法

通过实时定量聚合酶链反应测量110例急性MI患者、76例高血压患者和121例健康对照者血清中miR-499a的相对表达。通过实时等位基因鉴别分析对另外107例冠状动脉疾病患者进行MIR-499a基因分型。

结果

急性MI患者显示miR-499a相对表达较高(>105倍,p<0.001),在健康对照者和高血压患者中几乎检测不到。其曲线下面积为0.953,敏感性为97.2%,特异性为75.0%。ST段抬高型MI(STEMI)患者的miR-499a血清水平高于非STEMI患者。在所有测试的遗传模型下,MIR-499a变异与急性MI显著相关,但与高血压无关。作为一项新发现,在总体和分层分析中,miR-499a变异与其表达谱无关。

结论

循环miR-499a水平可能是一种有用的生物标志物,可在12小时内区分急性MI患者与健康受试者。其变异rs3746444 A/G与埃及人群急性MI和CAD易感性增加相关。

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