Association of the MIAT rs۱۸۹۴۷۲۰ Polymorphism with Ischemic Stroke Risk and MIAT Expression Levels in Blood after an Ischemic Stroke

Myocardial infarction associated transcript (MIAT) is a new disease-related lncRNA characterized by an improper expression in different ailments, such as ischemic stroke (IS), schizophrenia, diabetic complications, cancers, myocardial infarction, and cataracts. It is hypothesized that the MIAT rs۱۸۹۴۷۲۰ polymorphism is correlated with ischemic stroke risk and MIAT expression rate. We studied ۱۱۶ Iranian patients with clinically definite acute IS and ۱۱۶ ethnicity-, age-, and sex-matched controls. The tetra-primer ARMS-PCR method was applied for DNA genotyping. The susceptibility of IS and MIAT rs۱۸۹۴۷۲۰ polymorphism sites was analyzed. The MIAT expression in the blood was evaluated after RNA extraction, cDNA synthesis, and real-time PCR. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS. The mean age of IS patients was ۶۵.۹۰±۱۴.۴۴ years. The polymorphism of MIAT rs۱۸۹۴۷۲۰ was related to IS susceptibility in the recessive model (OR=۸.۵۱, ۹۵% CI=۱.۰۴-۶۹.۲۳, P=۰.۰۱). Furthermore, the co-dominant (OR=۰.۲۴, ۹۵% CI=۰.۰۷-۰.۷۶, P=۰.۰۰۹ for GT genotype), dominant (OR=۰.۲۶, ۹۵% CI=۰.۰۸-۰.۸۱, P=۰.۰۱),and over-dominant (OR=۰.۱۹, ۹۵% CI=۰.۰۷-۰.۵۲, P=۰.۰۰۰۵) models of the rs۱۸۹۴۷۲۰ were negatively associated with the risk of ischemic stroke. There was no correlation between rs۱۸۹۴۷۲۰ polymorphism and MIAT expression levels. We, also, detected a significant up-regulation of MIAT gene expression in IS stroke patients in comparison to the control group. ROC curves showed that MIAT might serve as a biomarker for diagnosing IS patients. The rs۱۸۹۴۷۲۰ polymorphism of the MIAT is correlated with the risk of IS but not with MIAT expression levels. In addition, the upregulation of blood-derived MIAT can be considered a diagnostic biomarker of IS.

Keywords:

Stroke , Long Non-Coding RNA , Polymorphism , Biomarkers , Real-Time PCR