Abstract
BackgroundEfforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population.MethodsBlood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0–24, 24–48, and 48–72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS.ResultsThe rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91–10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96–8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14–12.27) P = 0.030 and OR = 3.34 95% CL (1.13–9.85) P = 0.029].ConclusionThe rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.
Highlights
Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable
H19 rs217727 polymorphism has a positive association with the risk of IS We did not find any significant deviations from the Hardy-Weinberg equilibrium for rs217727 polymorphism in the control group
We found that the C allele of rs217727 was a significant protective factor against IS in the Iranian populations (C vs. T: Odds ratio (OR) = 0.62, 95% Confidence interval (CI): 0.39–0.99, P = 0.04)
Summary
Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. Stroke is one of the leading causes of death globally (accounting for 5.5 million deaths annually). Based on different molecular studies, the clarification of genetic biology, and epigenetic can facilitate the prediction and diagnosis of severe strokes [3]. Documents have increasingly revealed that dysregulated lncRNA expression levels can lead to various human diseases [4, 5] . Recent research works have shown that the expression of selected lncRNA changes over time after IS is detected in the blood of patients [9,10,11]. H19 lncRNA is the primary transcript of H19 locus; after birth, the abnormal expression of lncRNA H19 was presented as a potential diagnostic biomarker in different cancers [12]. LncRNA H19 is typically re-expressed in atherosclerotic plaque [12], and it can be activated under hypoxic conditions [13]
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