Long non-coding RNA H19 expression and functional polymorphism rs217727 are linked to increased ischemic stroke risk

Abstract

Background Efforts 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. Methods Blood 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. Results The 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]. Conclusion The 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.

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population. But ROC curve analysis revealed that the peripheral blood expression level of H19 could not be considered as a promising marker for the functional outcome and mortality prediction of IS patients, thus it cannot serve as a useful prognostic marker ( Rezaei et al, 2021 ).…”

Network Pharmacology and Bioinformatics Methods Reveal the Mechanism of Berberine in the Treatment of Ischaemic Stroke

“…Gao et al showed that lncRNA H19 acts as a competing endogenous RNA (ceRNA) of miR-19a-3p to target PTEN, inducing oxidative stress, increasing lactate dehydrogenase levels, increasing malondialdehyde levels, and decreasing superoxide dismutase activity, thus aggravating cerebral I/R injury [ 79 ]. A clinical study has shown that the expression levels of lncRNA H19 in patients increase within the first 24 h of stroke onset, which is closely related to the rs217727 functional polymorphism [ 80 ]. These data suggest that lncRNA H19 may be a potential biomarker for the diagnosis and treatment of ischaemic stroke.…”

The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases

“…Analysis of SNPs in the H19 gene revealed an increased risk for IS in patients that harbor a C to T variation of rs217727 or a C to A variation of rs4929984 [ 84 ]. Likewise, rs217727 polymorphism in the H19 gene has been associated with susceptibility to IS in a northern Chinese Han [ 133 ] and Iranian population [ 134 ]. In contrast, another study conducted in a southern Chinese Han population failed to correlate H19 rs217727 and rs4929984 gene polymorphisms with susceptibility to IS, even though these gene variants are associated with some risk factors for IS, such as diastolic blood pressure, coagulation function and homocysteine levels [ 135 ].…”