Abstract
Recent studies have explored the association between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and ischemic stroke (IS). In particular, the associations of rs2910164 (miRNA-146A), rs11614913 (miRNA-196A2), and rs3746444 (miRNA-499A) were intensively studied in IS. In this study, we investigated the associations between SNPs in miRNAs and IS including rs2910164, rs11614913, and rs3746444 in a Korean population. For a pilot study, we selected 19 SNPs in pre-miRNA region (including mature miRNA region) and genotyped in 140 IS patients and 240 control subjects using the Fluidigm Dynamic Array. Our pilot study showed a weak association of rs79402775 in miRNA-933 (p = 0.044) and a relatively strong association of rs35196866 in miRNA-4669 (p = 0.016) with IS. From the pilot study, we selected rs79402775, rs35196866, and rs7202008 (miRNA-2117; p = 0.055) as candidate miRNA SNPs on IS and further genotyped these SNPs in 264 IS patients and 455 control subjects using direct sequencing. In addition, we further analyzed the associations of rs2910164, rs11614913, and rs3746444 that have been intensively studied in previous studies. In the further analysis, we found the significant association between rs35196866 and IS (p = 0.0014 in additive model and p = 0.00015 in dominant model; p = 0.00037 in allele frequency analysis). However, the association between rs2910164, rs11614913, rs3746444, rs79402775, and rs7202008 and IS was not shown. These results suggest that miRNA-4669 may be involved in the susceptibility of IS.
Highlights
Stroke causes ~11% of all deaths worldwide and is the most common cause of death and adult disability [1]
Nineteen single-nucleotide polymorphisms (SNPs) selected on the pre-miRNA region of miRNAs were genotyped in these subjects using the Fluidigm Dynamic Array (192.24 Dynamic Array; Fluidigm, South San Francisco, CA, USA)
All SNPs were polymorphic, and the genotype distributions of the SNPs were in the Hardy-Weinberg equilibrium (HWE; p > 0:01; Table S1)
Summary
Stroke causes ~11% of all deaths worldwide and is the most common cause of death and adult disability [1]. In Republic of Korea, IS is the third most frequent cause of death after cancer and heart diseases in 2017 (Korea National Statistical Office; http://kostat.go.kr/portal/ eng/index.action). IS is a complex disease caused by multiple genetic and environmental risk factors [2]. In addition to the conventional risk factors, including hypertension, diabetes mellitus, smoking, hyperlipidemia, and hyperhomocysteinemia, variants of several susceptible genes have been recognized as genetic risk factors, showing the associations with IS, such as ACE, MTHFR, and APOE [3, 4]. The identified susceptible genes explained only a small portion of the total risk of IS, and reliable markers are still lacking
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