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.
Highlights
Stroke is known as one of the main reason of permanent disability and death all around the world [1]
In the ischemic stroke (IS) group, the triglyceride and homocysteine (HCY) levels tended to be higher than those observed in the controls, whereas high-density lipoprotein (HDL) cholesterol levels were lower at admission
We found that the independent risk factors of IS were smoking (OR = 2:27; 95% confidence intervals (CIs), 1.533.38), hypertension (OR = 6:05; 95% CI, 4.49-8.13), diabetes (OR =1.82; 95% CI, 1.17-2.82), triglycerides (OR = 1:16; 95% CI, 1.06-1.27), HDL-cholesterol (OR = 0:45; 95% CI, 0.30-0.68), and rs145204276 (OR = 2:27; 95% CI, 1.30-3.95) (Table S1)
Summary
Stroke is known as one of the main reason of permanent disability and death all around the world [1]. A number of different genetic determinants of IS risk have been identified in genome-wide association studies, with single-nucleotide polymorphisms (SNPs) in 9p21, PITX2, HDAC9, ABO, NINJ2, ALDH2, and TSPAN2, all being linked with stroke susceptibility [2]. These SNPs, are still thought to BioMed Research International account for less than half of all genetic susceptibility to IS, with a number of yet to be discovered genes contributing to the development of IS
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