Association between Genetic Polymorphism of The lncRNA MIAT rs1894720 with Ischemic Stroke Risk and lncRNA MIAT Expression Levels in The Blood after An Ischemic Stroke: A Case-Control Study.

Abstract

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. 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). 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). 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.