Abstract
A recent study of the ischemic stroke described the roles played by miRNAs in the downregulation of specific cell-cycle gene expression and it is thought to require the development of biomarkers for the prognostic of ischemic stroke. Here, we hypothesized that four miRNA polymorphisms (miR-10a, miR-27a, miR-34b/c, and miR-300) may affect stroke susceptibility and mortality. Blood samples were collected from 530 patients and 403 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and real-time PCR. We found that the miR-300 rs12894467 TC genotype and the dominant model (AOR: 2.069, p-value: 0.017; AOR: 1.931, p-value: 0.027) were significantly associated with an increased risk for the ischemic stroke subtype. In Cox proportional hazard regression models, the miR-10a rs3809783 A>T and miR-34b/c rs4938723 T>C polymorphisms were associated with the mortality rates among ischemic stroke patients. We found that a miR-300 polymorphism was associated with increased ischemic stroke susceptibility among the Korean population. Additionally, polymorphisms in miR-10a and miR-34b/c were associated with the increased or decreased mortality of ischemic stroke patients. This study marks the first report of an association between ischemic stroke and miRNA polymorphisms (miR-10aA>T, miR-27aT>C, miR-34b/cT>C, and miR-300T>C) in the Korean population.
Highlights
Ischemic stroke is caused by several gene–gene and gene–environment interactions [1,2] and can be affected by genetic and environmental factors, including advanced age, diabetes mellitus (DM), family or personal history of stroke, high cholesterol, smoking, hypertension (HTN), hyperlipidemia, and metabolic syndrome (MetS), among which DM, HTN, smoking, and hyperlipidemia are considered to be the primary contributors [3]
Ischemic stroke was defined as a stroke with evidence of cerebral infarction in clinically relevant areas of the brain according to magnetic resonance imaging (MRI) scan finding
We performed a Cox proportional analysis, and the results showed that the miR-10a rs3809783 A>T and miR-34b/c rs4938723 T>C polymorphisms were associated with the five-year mortality rates among ischemic stroke patients
Summary
Ischemic stroke is caused by several gene–gene and gene–environment interactions [1,2] and can be affected by genetic and environmental factors, including advanced age, diabetes mellitus (DM), family or personal history of stroke, high cholesterol, smoking, hypertension (HTN), hyperlipidemia, and metabolic syndrome (MetS), among which DM, HTN, smoking, and hyperlipidemia are considered to be the primary contributors [3]. Many previous studies have demonstrated that the expression levels of target genes can be regulated by several miRNAs [15,16,17], and miRNAs have been examined in several diseases, including stroke [18,19,20,21,22,23]. These studies have provided evidence for the functions of miRNAs and have indicated that miRNA biosynthesis may contribute to important physiological and pathological processes [24,25]. As miRNA studies have progressed, in vivo and human studies have reported the abnormal expression of miRNAs associated with stroke [26,27,28]
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