Abstract
BackgroundRecent evidence suggests that long non-coding RNAs (lncRNAs) are key regulators in the pathological process of ischemic stroke (IS). Maternally expressed gene 3 (MEG3) was observed to be up-regulated in IS, acting as a competing endogenous RNA for miR-181b to regulate ischemic brain injury. The purpose of this study was to evaluate the association of tagSNPs in MEG3 (i.e., rs7158663 and rs4081134) and miR-181b rs322931 with IS risk.MethodsGenomic DNA was extracted from blood samples of 509 patients with IS and 668 healthy controls. Genotyping of MEG3 rs7158663, rs4081134, and miR-181b rs322931 was performed by TaqMan assay. The transcriptional activity was measured using the Dual-Luciferase Reporter Assay kit.ResultsSingle-site analysis revealed a significantly higher risk of IS being associated with miR-181b rs322931 CT and CT/TT genotypes (CT vs. CC: adjusted OR = 1.48, 95% CI: 1.13–1.95, P = 0.005; CT/TT vs. CC: adjusted OR = 1.52, 95% CI: 1.17–1.97, P = 0.002). Combined analyses revealed that combined genotypes (rs7158663 GG + rs322931 CT/TT and rs7158663 AG/AA + rs322931 CT/TT) increased IS risk compared to genotypes of rs7158663 GG + rs322931 CC. Stratification analyses showed that patients carrying miR-181b rs322931 CT/TT genotypes had higher levels of low-density lipoprotein cholesterol (LDL_C) (P = 0.01). Moreover, results from logistic regression analysis showed that rs322931 CT/TT genotypes were risk factors besides hypertension, total cholesterol, triglyceride, and LDL_C. Further dual-luciferase reporter assay showed that the rs322931 T allele had lower levels of luciferase activity than the rs322931 C allele.ConclusionThese findings indicate that miR-181b rs322931 may singly or jointly contribute to the risk of IS.
Highlights
Stroke is the major cause of morbidity and mortality worldwide, with about 15 million new cases and 5 million death each year [1, 2]
Patients with ischemic stroke (IS) had a higher prevalence of hypertension and diabetes mellitus and higher levels of Total cholesterol (TCH), TG, and low-density lipoprotein cholesterol (LDL-C)
Association between polymorphisms in Maternally expressed gene 3 (MEG3)/miR-181b and IS risk The genotype frequencies of MEG3 rs7158663, rs4081134 and miR-181b rs322931 were in Hardy-Weinberg equilibrium (HWE) in both cases and controls (P > 0.05). miR-181b rs322931 CT and CT/TT genotypes were more frequent in IS patients than in controls (33.4 vs. 26.8% and 38.1 vs. 29.2%)
Summary
Stroke is the major cause of morbidity and mortality worldwide, with about 15 million new cases and 5 million death each year [1, 2]. IS is a complex disorder, involving in a series of risk factors including hypertension, dyslipidemia, obesity, diabetes, smoking as well as genetic factor [8,9,10,11]. Adults with both high triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), and high low-density lipoprotein cholesterol (LDL-C), those with diabetes, have an increased risk of IS [12]. Expressed gene 3 (MEG3) was observed to be up-regulated in IS, acting as a competing endogenous RNA for miR-181b to regulate ischemic brain injury. The purpose of this study was to evaluate the association of tagSNPs in MEG3 (i.e., rs7158663 and rs4081134) and miR-181b rs322931 with IS risk
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