Abstract
BackgroundThe microRNA-17-92 (miR-17-92) cluster is one of the most extensively studied miRNA clusters. Abnormal expression of the cluster has been found to play important role in different kinds of human diseases, including ischemic stroke (IS). The aim of our study was to investigate the association between three polymorphisms (rs1491034, rs9301654 and rs982873) in the promoter of the miR-17-92 cluster and risk of IS.MethodsThree hundred and ninety-eight patients with IS and 397 control subjects were included. The genotypes of the three polymorphisms were determined by Snapshot SNP genotyping assay. Relative expression of the cluster in peripheral blood mononuclear cells (PBMCs) of cases and controls were examined by quantitative real-time PCR.ResultsSignificant association between rs9301654 polymorphism and risk of IS were observed basing on genotype, model and allele analyses (GA vs. AA: adjusted OR = 0.63, 95% CI: 0.41~0.97, P = 0.037; GG vs. AA: adjusted OR = 0.23, 95% CI: 0.07~0.78, P = 0.018; GA + GG vs. AA: adjusted OR = 0.57, 95% CI: 0.38~0.87, P = 0.009; GA + AA vs. GG: adjusted OR = 0.27, 95% CI: 0.08~0.89, P = 0.032; G vs. A: adjusted OR = 0.58, 95% CI: 0.40~0.83). Haplotype analysis showed that TGC and TGT haplotypes were associated with decreased risk of IS (OR = 0.59, 95% CI: 0.40~0.87, P = 0.007 for TGC haplotype; OR = 0.21, 95% CI: 0.06~0.75, P = 0.009 for TGT haplotype). Importantly, we found the expression of miR-17-5p was significant higher while miR-19a-3p was significant lower in patient with IS compared with the control group (P < 0.01), and patients with rs9301654GG or GA genotype displayed lower level of miR-19a-3p compared with the AA genotype (P < 0.01).ConclusionsOur findings indicated that rs9301654 polymorphism in the promoter of miR-17-92 cluster may be associated with susceptibility of IS in the Chinese population. However, we found that rs9301654 polymorphism and its respective gene expression did not demonstrate consistent association with IS in the Chinese population. Further studies such as gene-gene interaction are warranted to reveal the role of miR-19a and its regulatory genes in the etiology of IS.
Highlights
The microRNA-17-92 cluster is one of the most extensively studied miRNA clusters
We found that TGC and TGT haplotypes were associated with decreased risk of ischemic stroke (IS) (OR = 0.59, 95% confidence interval (CI): 0.40~0.87, P = 0.007 for TGC haplotype; Odds ratio (OR) = 0.21, 95% CI: 0.06~0.75, P = 0.009 for TGT haplotype)
OR odds ratio, CI confidence interval expression of the miR-17-92 cluster in the control group and the IS group were examined and we found that the relative expression of miR-17-5p was significant higher while the miR-19a-3p was significant lower in patient with IS compared with the control group (Fig. 2; both P < 0.01)
Summary
The microRNA-17-92 (miR-17-92) cluster is one of the most extensively studied miRNA clusters. Abnormal expression of the cluster has been found to play important role in different kinds of human diseases, including ischemic stroke (IS). The aim of our study was to investigate the association between three polymorphisms (rs1491034, rs9301654 and rs982873) in the promoter of the miR-17-92 cluster and risk of IS. The incidence of stroke is still serious in China, with about 2.6 million new stroke patients and 1.6 million stroke relate death each year [3]. In the past several years, a large numbers of IS related susceptibility genes such as growth arrest-specific transcript 5, cluster of differentiation 40, interleukin 6 and tumor necrosis factor α have been identified [7,8,9,10]
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