Abstract
We conducted a case-control study investigating the association between the single-nucleotide polymorphism rs2910164 in microRNA (miR)-146a and the risk and prognosis of stroke. We recruited a total of 1139 ischemic stroke patients and 1585 sex- and age-matched control subjects. After a median follow-up period of 4.5 years, 1071 of these ischemic stroke patients were then recruited for a prospective study. Our study revealed that rs2910164 was not associated with ischemic stroke incidence (odds ratio = 1.00; 95% confidence interval (CI) = 0.80–1.24; p = 0.985) by multivariate logistic regression. Meta-analysis of our case-control study and three others on Asian populations also suggested that there was no relationship between rs2910164 and ischemic stroke incidence. The significance of differences in long-term outcomes was examined by the log-rank test of the respective comparison groups. The prospective study showed that rs2910164 led to a 1.56-fold increased risk of stroke recurrence (hazard ratio (HR) = 1.56; 95% CI = 1.10–2.20; p = 0.013) and a 2.13-fold increased risk of death caused by cardiovascular disease or stroke (Csdeath) (HR = 2.13; 95% CI = 1.31–3.46; p = 0.002). The independent association of rs2910164 with stroke prognosis was evaluated using Cox regression models. Therefore, rs2910164 appears to be a strong predictor of stroke prognosis but not of stroke incidence in Asian populations.
Highlights
Stroke has a limited therapeutic time window and a very high rate of recurrence, and is a leading cause of death and constitutes a heavy economic burden in many countries, including China [1,2,3,4]
Multiple susceptibility genes have been demonstrated to have a relationship with an enhanced risk of stroke or worse stroke prognosis, including F5, angiotensin-converting enzyme (ACE), methylenetetrahydrofolate reductase (MTHFR), serpin peptidase inhibitor 1 (SERPINE1), apolipoprotein E (APOE) [7], cytochrome P450 2C19 (CYP2C19) [8], and platelet-derived growth factor D (PDGF-D) [9], as well as chromosome 12p13 variants [10]
Genetic alterations in miR sequences impact on precursor processivity, maturation, expression, and influence the expression of target mRNAs [11,12,13]. miRNAs are important in biological processes including cell differentiation, proliferation, growth, stress resistance, and metabolism, as well as the pathophysiology of neurodegenerative disease, cancer, and cardiovascular disease [14,15,16]
Summary
Stroke has a limited therapeutic time window and a very high rate of recurrence, and is a leading cause of death and constitutes a heavy economic burden in many countries, including China [1,2,3,4] It is a multifactorial disease affected by environmental and genetic risk factors including hypertension, diabetes mellitus, smoking, hyperlipidemia, and hyperhomocysteinemia [5,6]. Emerging evidence indicates that circulating miRNAs may be novel biomarkers for the diagnosis and prognosis of stroke [17,18] This reflects their role in modulating transcriptional programs that affect the processes of atherosclerosis, including endothelial integrity, inflammation, and extracellular matrix remodeling [19,20]
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