DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

Abstract

Objective. Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. Methods. Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. Results. A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups ( P < 0.05 ). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups ( P < 0.05 ). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups ( P < 0.05 ). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups ( P < 0.05 ). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group ( P < 0.05 ). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group ( P < 0.05 ). Conclusion. The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

A Prediction Model for Neurological Deterioration in Patients with Acute Spontaneous Intracerebral Hemorrhage

“…At admission, data collected included the patients’ age, gender, Body Mass Index (BMI), time of onset to emergency department (ED), SBP on admission, diastolic blood pressure (DBP) on admission, body temperature, baseline hematoma volume, history of high blood pressure (HBP), smoking history, drinking history, other medical history, serum sodium, serum calcium, hemoglobin (Hb), white blood cell (WBC) count, platelet (PLT) count, activated partial thromboplastin time, international normalized ratio (INR), fibrous protein, blood glucose, serum creatinine, troponin, total cholesterol (TCHO), low-density lipoprotein cholesterin (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), bleeding part, IVH, IVH expansion, subarachnoid expansion, DBP change in 24 h, SBP change in 24 h, hematoma volume change in 24 h, blend sign, spot sign, leukodystrophy, lacuna cerebri, and brain atrophy (any central or cortical reduction). The hematoma volume was calculated according to the Coniglobus formula ( 19 ): V = a × b × c × 1/2 (where a represents the longest diameter of hematoma at the level of maximum hematoma area, b represents the longest diameter perpendicular to the longest diameter at the level of maximum hematoma area, and c represents the number of layers with bleeding in CT images). The proportion of missing values for most of the included variables was less than 7%, which were filled using multiple imputation.…”

Epigenetic mechanisms and potential therapeutic targets in stroke

“…44 In patients with spontaneous ICH, hypomethylation of the dedicator of cytokinesis 1 (DOCK1) promoter was associated with increased DOCK1 expression, hematoma volume, and worsened rehabilitative outcomes. 45…”

“…44 In patients with spontaneous ICH, hypomethylation of the dedicator of cytokinesis 1 (DOCK1) promoter was associated with increased DOCK1 expression, hematoma volume, and worsened rehabilitative outcomes. 45 In ischemic stroke patients, several studies showed significant correlation between blood DNA methylation and post-stroke outcome. In particular, blood methylation patterns in solute carrier family 6 member 4 (SLC6A4) have been associated with the risk of stroke recurrence, post-stroke depression, and neurologic deterioration.…”

Retracted: DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”