Genetic Variants of lncRNA GAS5 Contribute to Susceptibility of Ischemic Stroke among Southern Chinese Population

Abstract

Emerging evidence suggests that the long noncoding RNA (lncRNA) growth arrest special 5 (GAS5) plays crucial roles in the pathogenesis of ischemic stroke (IS). The current research is aimed at assessing the correlation between two functional GAS5 variants (rs145204276 and rs55829688) and susceptibility to IS in a Han Chinese population. This study genotyped the two GAS5 variants in 1086 IS patients as well as 1045 age-matched healthy controls by using an improved multitemperature ligase detection reaction (iMLDR-TM) genotyping technology. We observed a considerable change in the frequencies of the rs145204276 allele and genotype among the IS patients and healthy control group. The del-T haplotype was substantially more prevalent in the IS cases compared to the control individuals. When study participants were stratified according to environmental factors, we found that the rs145204276 del allele was correlated with a higher risk of IS in male, smokers, hypertensive, and those ≥65 years old. Additional stratification conforming to IS subtypes exhibited that individuals carrying the rs145204276 del allele conferred a higher risk of expanding a larger artery atherosclerosis stroke subset. Moreover, there was a significant association between the rs145204276 del allele and elevated expression of GAS5 in IS patients. In contrast, the frequency of the allele related to rs55829688 was not statistically correlated with IS in all analysis. Our study supports a model wherein the rs145204276 variant in the GAS5 lncRNA is associated with IS risk, thus representing a potentially viable biomarker for IS prevention and treatment.

Block Copolymer Nanomicelle-Encapsulated Curcumin Attenuates Cerebral Ischemia Injury and Affects Stem Cell Marker Expression by Inhibiting lncRNA GAS5

“…Stroke has become the most common cause of death in China [1] of which IS accounts for the vast majority, reaching 70% to 80% [2]. At present, the effective treatment methods for IS are mainly to open arteries and restore blood flow as soon as possible [3,4] including intravenous thrombolysis and mechanical clot thrombectomy. However, due to the limitation of effective treatment time and other conditions, the vast majority of IS patients fail to receive these treatments.…”

Long noncoding RNA GAS5 and miR-137 and two of their genetic polymorphisms contribute to acute ischemic stroke risk in an Egyptian population

“…Other SNPs in GAS5 have been previously linked to AIS risk, like a correlation between rs145204276 del allele and increased AIS risk among a Chinese population. 32 Similarly, rs2067079 has been reported to influence lncRNA GAS5 expression level in multiple sclerosis (MS) patients with rs2067079 TT genotype. 15 However, the current study showed no similar effect of rs2067079 on lncRNA GAS5 expression which could be attributed to the relatively small sample size and the different clinical subtypes of AIS that the subjects had.…”

Epigenetic mechanisms and potential therapeutic targets in stroke

“…GAS5 increased in the blood of stroke patients where it was associated with increased stroke risk and poor rehabilitative outcomes in hypertensive, diabetic, and aged stroke patients. 127,128…”

“…GAS5 increased in the blood of stroke patients where it was associated with increased stroke risk and poor rehabilitative outcomes in hypertensive, diabetic, and aged stroke patients. 127,128 The lncRNA maternally expressed gene 3 (MEG3) was upregulated in the core, but downregulated in the penumbra following transient MCAO in rodents. 129,130 MEG3 has been shown to play a role in the recruitment of EZH2 and the PRC2 component jumonji and AT-rich interaction domain containing 2 (JARID2) and histone H3 methylation.…”