RESUMO
OBJECTIVE: Genetic aspects can play an essential role in the occurrence and development of ischemic stroke (IS). Rs1894720 polymorphism is one of the eight single nucleotide polymorphisms (SNPs) in the long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) locus. The aim of study is the lncRNA MIAT rs1894720 polymorphism decreases IS risk by reducing lncRNA MIAT expression. MATERIALS AND METHODS: In this case-control study, we studied 232 Iranian patients and 232 controls. The blood samples were collected from patients admitted at different times after stroke symptoms. We enrolled 80, 78, and 74 patients who arrived at the hospital between 0-24, 24-48, and 48-72 hours after the first appearance of symptoms, respectively. DNA genotyping was done by the tetra-primer ARMS-PCR method. Circulating MIAT levels were evaluated by real-time polymerase chain reaction (PCR). RESULTS: The GT genotype of MIAT rs1894720 showed a significant association with the risk of IS (OR=3.53, 95% CI=2.13-5.84, P<0.001). MIAT expression was higher relative to the control within the first hours after IS. The MIAT levels in IS patients with rs1894720 (GT) were significantly lower relative to patients who had the GG and TT genotypes. Linear regression model indicated a significant correlation between MIAT expression with atherosclerotic risk factors and types of stroke in IS patients. Receiver operating characteristic (ROC) curve analysis showed that the level of lncRNA MIAT after IS could be diagnostic with an area under the curve (AUC) of 0.82. The sensitivity and specificity were 80.17 and 67.24%, respectively (P<0.001). CONCLUSION: Our study demonstrated that the MIAT rs1894720 polymorphism (GT) might increase the risk of IS in the Iranian population. MIAT expression was up-regulated in our IS patients. Hence, it could be a diagnostic biomarker for IS.
RESUMO
BACKGROUND: Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population. METHODS: Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0-24, 24-48, and 48-72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS. RESULTS: The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91-10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96-8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14-12.27) P = 0.030 and OR = 3.34 95% CL (1.13-9.85) P = 0.029]. CONCLUSION: The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.
