Long Noncoding RNAs MALAT1 and ANRIL Gene Variants and the Risk of Cerebral Ischemic Stroke: An Association Study

Abstract

Cerebral ischemic stroke (CIS) is one of the primary causes of death worldwide and a major cause of long-term disability. Long noncoding RNAs (lncRNAs) have emerged as crucial mediators in the pathology of CIS; however, their potential importance is yet to be discovered. Herein, we examined the association of four single-nucleotide polymorphisms (SNPs) with the risk of CIS, their correlation with the lncRNAs, MALAT1 and ANRIL, expression, and the potential of serum MALAT1 and ANRIL as biomarkers for CIS. A total of 100 CIS patients and 100 healthy controls were recruited in the study. Genotyping and expression analysis of MALAT1 and ANRIL SNPs were carried out by qPCR. The present results showed that serum MALAT1 was downregulated, while serum ANRIL was overexpressed in CIS patients, relative to controls. MALAT1 downregulation discriminated CIS patients from controls by receiver-operating-characteristic analysis. Moreover, serum ANRIL denoted good diagnostic accuracy. MALAT1 rs619586 AA and rs3200401 CT, TT were associated with increased CIS risk, whereas ANRIL rs10965215 GG was found to be protective. The studied ANRIL rs10738605 polymorphism was not associated with CIS susceptibility. Notably, the G variant of MALAT1 rs619586 demonstrated a higher serum MALAT1 expression level. Multivariate logistic regression analysis revealed serum MALAT1 as well as MALAT1 rs3200401 CT + TT as independent predictors of CIS. Additionally, a negative association was found between the serum MALAT1 level and the National Institutes of Health Stroke Scale score. In conclusion, MALAT1 rs619586 and rs3200401 and ANRIL rs10965215 are novel prospective noninvasive diagnostic biomarkers for CIS predisposition.

Association Between Malat1 Rs4102217-Polymorphic Variant and Ishemic Atherothrombotic Stroke Development in People With Increased Body Mass Index

“…The opposite results were obtained by Nevine Fathy et al, according to their study MALAT1 rs619586 AA and rs3200401 CT, TT was associated with an increased risk of cerebral ischemic stroke [18]. The results of our study confirm the conclusions of other scientists on the important role of polymorphisms in the gene of long non-coding RNA MALAT1.…”

Association of Long Non-Coding RNA Malat1 with Serum Levels of Interleukin-1 Beta and Vitamin D in Patients with Ischemic Stroke

“…Different experimental and clinical research has shown the anti-inflammatory and anti-apoptotic roles of Malat1 in the brain [11][12][13]. The downregulation of lncRNA Malat1 in IS patients has been reported in previous studies [12,14]. Ren et al demonstrated that Malat1 expression was inversely associated with the National Institutes of Health Stroke Scale (NIHSS) score and the expression of pro-inflammatory factors (including TNF-α, CRP, IL-6, IL-22, and IL-8) on the first day after stroke [12].…”

“…Ren et al demonstrated that Malat1 expression was inversely associated with the National Institutes of Health Stroke Scale (NIHSS) score and the expression of pro-inflammatory factors (including TNF-α, CRP, IL-6, IL-22, and IL-8) on the first day after stroke [12]. Fathy et al in 2021 also reported the downregulation of Malat1 in IS patients with a negative association with stroke severity [14] The soluble glycoproteins that are produced by microglia, astrocytes, endothelial cells, and neurons in response to damaged brain tissue are cytokines. Cytokines clearly play a key role in the pathophysiology of stroke, and a high ratio of pro-inflammatory to anti-inflammatory cytokines is associated with larger infarct volume and poorer functional outcomes in IS patients [15].…”

The Relationship between MALAT1 Polymorphism rs3200401 C > T and the Risk of Overall Cancer: A Meta-Analysis

“…One study reported a tendency that serum MALAT1 expression levels of the TT genotype and CT + TT genotype were higher than that of the CC genotype in CRC patients [36]. A similar trend was found in serum MALAT1 expression levels between rs3200401 C>T and cerebral ischemic stroke [37]. Li et al found that MALAT1 mRNA was overexpressed in CRC tissues according to the Oncomine expression profiling database [38].…”