Antiplatelet therapy may improve the prognosis of patients with moyamoya disease: a 12-year retrospective study.

OBJECTIVES: The clinical value of antiplatelet therapy (APT) for moyamoya disease (MMD) remains controversial. Our study attempts to clarify the value of APT in this disease. METHODS: We collected basic information, treatment strategies, and prognostic information on patients with MMD from 2010 to 2022 at our center. The data were divided into two groups, depending on whether APT was used or not, and compared by Pearson Chi-Square, Fisher's exact test, or Wilcoxon rank-sum test. We used propensity scores or inverse probability of treatment weighting to balance the covariates. Following this, we performed a meta-analysis of APT use in MMD. RESULTS: 177 patients were enrolled, with a median follow-up of 41.1 months. APT did not affect the prognosis of patients with perioperative MMD, ischemic MMD, or asymptomatic MMD (P > 0.05), without increasing cerebral hemorrhagic risk. In contrast, APT was found to reduce mortality among patients with hemorrhagic MMD (P = 0.019), without affecting functional status, increasing stroke risk, or causing intracerebral hemorrhage (P > 0.05). But the small group cannot show the effect of APT. Our meta-analysis included nine articles involving 28,925 patients with MMD. It showed that APT could reduce stroke risk (odds ratio, OR = 0.57, 95% CI 0.49 to 0.65) and the Modified Rankin Scale (mRS) (weighted mean difference, WMD = - 0.07, 95% CI 0.14-0.00) during follow-up. The cohort study has limited weight (1.97% and 19.29%) in the meta-analysis. CONCLUSION: Although the limited number of included documents, APT could be beneficial to the prognosis of MMD.

mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = -0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance.

Acute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia characterized by unrestricted megakaryoblast proliferation and poor prognosis. Thrombopoietin receptor c-Mpl is a primary regulator of megakaryopoeisis and a potent mitogenic receptor. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however, the role of c-Mpl in AMKL progression remains largely unexplored. Here, we identified increased expression of a c-Mpl alternative splicing isoform, c-Mpl-del, in AMKL patients. We found that c-Mpl-del expression was associated with enhanced AMKL cell proliferation and chemoresistance, and decreased survival in xenografted mice, while c-Mpl-del knockdown attenuated proliferation and restored apoptosis. Interestingly, we observed that c-Mpl-del exhibits preferential utilization of phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in upregulation of GATA1 and downregulation of DDIT3-related apoptotic responses conducive to AMKL chemoresistance and proliferation. Thus, this study elucidates the critical roles of c-Mpl alternative splicing in AMKL progression and drug resistance, which may have important diagnostic and therapeutic implications for leukemia accelerated by c-Mpl-del overexpression.

Ring Finger Protein 213 in Moyamoya Disease With Pulmonary Arterial Hypertension: A Mini-Review.

Moyamoya disease (MMD), most often diagnosed in children and adolescents, is a chronic cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Recently, many investigators show a great interest in MMD with pulmonary arterial hypertension (PAH). Ring finger protein 213 (RNF213) is a major susceptibility gene for MMD and also has strong correlations with PAH. Therefore, this review encapsulates current cases of MMD with PAH and discusses MMD with PAH in the aspects of epidemiology, pathology, possible pathogenesis, clinical manifestations, diagnosis, and treatment.

Prognosis associated with asymptomatic intracranial hemorrhage after acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: It remains inconclusive whether asymptomatic intracranial hemorrhage (aICH) after acute ischemic stroke is innocuous. We aimed to conduct a meta-analysis assessing the relationship between the aICH and poor neurological outcomes. METHODS: We searched PubMed, EMBASE and Web of Science from their inception to 30 November 2021 and performed a meta-analysis on the association between the aICH and neurological prognosis after acute ischemic stroke at 3 months, including poor outcomes (modified Rankin Scale [mRS] score ≥ 2 or mRS ≥ 3) and mortality. RESULTS: Fourteen studies were included in the analysis, reporting on a total of 10,915 participants after acute ischemic stroke. The risks of poor outcome (mRS ≥ 2 or mRS ≥ 3) in patients with aICH were significantly higher than patients without ICH (OR 1.70, 95% CI 1.33-2.18; OR 1.43, 95% CI 1.20-1.70, respectively), based on adjusted data. The difference between the two groups was not significant for mortality. The results of subgroup analysis showed aICH were associated with higher ratio of mild poor prognosis (mRS ≥ 2) (OR 1.59, 95% CI 1.11-2.27), but it had no association with functional dependence (mRS ≥ 3) after recanalization. No significant influence of aICH on poor outcome (mRS ≥ 3) was found in non-recanalization group. Further stratified analysis revealed that only aICH with patients receiving endovascular therapy (EVT) could increase the risk of mild poor prognosis (mRS ≥ 2) at 3 months. CONCLUSIONS: Our results indicate that compared with patients without ICH, those who developed aICH during the acute stage of ischemic stroke had an increasing risk of worse outcome, especially in patients with endovascular therapy.

Immunoadsorption with staphylococcal protein A column in autoimmune encephalitis.

BACKGROUND: Early treatment has a positive effect on autoimmune encephalitis. However, different treatments have individual differences and corresponding contraindications in the clinical. Few reports have described the application of immunoadsorption with Staphylococcal Protein A Column (SPA-IA) in neuroimmune diseases. We aimed to observe the safety and efficiency of SPA-IA in autoimmune encephalitis. PATIENTS AND METHODS: We retrospectively analyzed three cases of autoimmune encephalitis wherein the first-line treatment was ineffective or contraindicated. The clinical features and prognosis during and after SPA-IA are described in detail. RESULTS: All patients were definitely diagnosed with autoimmune encephalitis. After treated with SPA-IA, all antibody titers, except for the serum antibody titer in Patient 2, were markedly decreased in both the cerebral spinal fluid and serum. The mean fibrinogen levels before and after SPA-IA were stable, and there were no clinical bleeding events. The modified Rankin Scale scores and their symptoms improved significantly after the last SPA-IA session or 3 months later. CONCLUSIONS: SPA-IA may be a viable, efficacious, and safe treatment alternative for autoimmune encephalitis with contraindications to traditional treatment or poor response.

Mutations of RNF213 are responsible for sporadic cerebral cavernous malformation and lead to a mulberry-like cluster in zebrafish.

Although familial forms of cerebral cavernous malformation are mainly attributed to three CCM genes (KRIT1, CCM2 and PDCD10), no mutation is identified in sporadic cerebral cavernous malformation cases with a unique lesion, indicating additional genes for sporadic cerebral cavernous malformation. To screen the candidate genes, we conducted whole exome sequencing in 31 sporadic cerebral cavernous malformation patients and 32 healthy controls, and identified 5 affected individuals carrying 6 heterozygous deleterious mutations in RNF213 but no RNF213 mutation in healthy individuals. To further confirm RNF213 was associated with cerebral cavernous malformation, we generated rnf213a homozygous knockout zebrafish and found mutation of rnf213a in zebrafish led to a mulberry-like cluster of disordered-flow vascular channels which was reminiscent of human cerebral cavernous malformation. In addition, we revealed kbtbd7 and anxa6 were significantly downregulated due to rnf213a mutation through transcriptomic sequencing and RT-qPCR analysis. Based on the mulberry-like phenotype partly rescued by mRNA of kbtbd7 as well as anxa6, we suggested that rnf213a promoted mulberry-like cluster via downregulation of kbtbd7 and anxa6. Altogether, we firstly demonstrate RNF213is a novel candidate gene for sporadic cerebral cavernous malformation and the mutation of rnf213a is responsible for the mulberry-like cluster in zebrafish.

The metagenomic next-generation sequencing in diagnosing central nervous system angiostrongyliasis: a case report.

BACKGROUNDS: The incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests. CASE PRESENTATION: A 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations. CONCLUSIONS: The case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

Prevalence of RNF213 variants in symptomatic intracranial arterial stenosis/occlusion in China.

The ring finger protein 213 gene (RNF213) rs112735431 was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. We conducted a case-control study to examine the prevalence and correlates of the RNF213 rare variants in Chinese patients with symptomatic ICASO. A total of 503 cases including 390 ischemic stroke patients (ICASO-IS), 113 intracranial hemorrhage patients (ICASO-ICH) and 227 control subjects were recruited. The snapshot technique was used for RNF213 rare variants analysis, including rs112735431, rs148731719, rs37144111 and rs138130613. Moreover, a meta-analysis was performed to explore the relationship between RNF213 variants and ICASO in Asian. In our case-control study, we found that the rs138130613 variant was significantly associated with ICASO-IS (OR = 9.92, 95% CI 1.24-79.19, p = 0.03). The mean age of first ischemic stroke onset of variant carriers was earlier than the noncarriers (51.3 ± 18.0 versus 66.0 ± 12.9 years old, p = 0.02), but the conventional atherosclerotic risk factors and the characteristics of artery stenosis did not differ between them. In addition, the meta-analysis showed significant association between the rs112735431 polymorphism and the ICASO or ICASO-IS, and this variant was found more often in women and young-onset patients in Asia. This study suggests that the RNF213 rs112735431 and rs138130613 are genetic risk variants for ischemic stroke with intracranial artery stenosis/occlusion in China and rs112735431 is also associated with the high risk of ICASO in Asia. Further large-scale investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of symptomatic ICASO.

What is the best option to manage the bedside teaching for Neurology Clerkship -- Demonstration, Simulation or WeChat teaching?

This article was migrated. The article was marked as recommended. Background: Neurological clerkship is an important but challenging part of the neurology curriculum, and bedside teaching is essential for clerks to integrate complex theories and skills into practice. Objective: This study aimed to investigate the three bedside teaching methods as modified bedside demonstration, simulation via standard patients as well as WeChat-assisted teaching during neurological clerkship, in order to identify the optimal method. Design: The4 th-year medical students were enrolled during their neurological clerkship. Bedside teaching on topics of acute ischemic stroke, acute myelitis and myasthenia gravis were delivered in a random order of demonstration, simulation and WeChat-assisted teaching. A questionnaire was assigned to each participant at the end of the two-week clerkship to rank the three methods based on their general impression, as well as detailed assessment of clinical abilities and attitudes. Results: A total of 112 clerks were enrolled and 98 were eligible for analysis. For both general and overall ranking, simulation was the most approved bedside teaching method while WeChat-assisted teaching took the least approval among the three. A majority of participants preferred simulation because of the significant improvement on interpretation of diseases, interest in neurology, diagnostic skills, clinical skills, communication skills, empathy and protection of privacy (P＜0.05). Demonstration was considered to benefit performance in examination (P=0.009). The ranking of the three methods revealed different consistency between general impression and detailed assessment. More participants tended to underestimate themselves in simulation but to overestimate themselves in WeChat-assisted teaching (P=0.000). Conclusions: Simulation outweigh WeChat-assisted teaching and demonstration by promoting clinical skills, as well as inspiring students' academic interest, compassion and empathy in both the general ranking and the overall ranking. Clerks were tended to underestimate their clinical competence in simulation but overestimate themselves in WeChat-assisted teaching.

AND score: a simple tool for predicting infection in acute ischemic stroke patients without a ventilator in the Chinese population.

OBJECTIVE: We aimed to develop a simple and user-friendly scoring system to predict all-cause hospital-acquired infections (HAIs) after acute ischemic stroke (AIS) in the Chinese population. METHODS: AIS patients from a retrospective cohort study at our center were included from January 2016 to December 2018. HAIs were diagnosed based on the current criteria from Ministry of Health of the People's Republic of China. Stepwise logistic regression models were performed to screen independent predictors of HAI after AIS. A scoring system was developed by including each of the above significant predictors. RESULTS: Among 1211 patients, 76 patients (6.28%) developed HAI. Age, baseline National Institute of Health stroke scale (NIHSS) score, and dysphagia were independent predictors of HAI. For the AND score, A refers to age, N refers to NIHSS, and D refers to dysphagia. The AND score showed a high area under the receiver operating characteristics (AUROC) curve (0.679), which comprised age (65-74 years was 4 points, 75-84 years was 6 points, ≥85 years was 8 points), NIHSS score ≥10 (5 points), and dysphagia (6 points). CONCLUSIONS: We developed a simple scoring system to predict all-cause infections after AIS patients without a ventilator in the Chinese population.

Bilateral cerebral infarction associated with severe arteriosclerosis in the A1 segment: a case report.

Large artery atherosclerosis and cardioembolism are the two major subtypes of ischemic stroke. We herein describe a 75-year-old man with acute complete cerebral infarction in the typical territories of the bilateral anterior cerebral artery (ACA) and left middle cerebral artery. Brain magnetic resonance angiography showed that the right A1 segment of the ACA was affected by severe arteriosclerosis and that the right ACA other than the A1 segment was compensated by the left ACA through the anterior communicating artery. Acute cardioembolism only occluded the left anterior circulation but simultaneously blocked the right ACA due to decompensation. We presume that the bilateral cerebral infarctions were caused by chronic atherosclerosis and acute cardioembolism.

Altered expression of circular RNAs in human placental chorionic plate-derived mesenchymal stem cells pretreated with hypoxia.

BACKGROUND: Hypoxic preconditioning alters the biological properties of mesenchymal stem cells (MSCs). It is not known whether this process has an effect on circular RNAs (circRNAs) in MSCs. METHODS: Human placental chorionic plate-derived MSCs (hpcpMSCs) isolated from the same placentae were classed into two groups: hypoxic pretreated (hypoxia) group and normally cultured (normoxia) group. The comparative circRNA microarray analysis was used to determine circRNAs expression and verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in the two groups. RESULTS: One hundred and two differentially expressed circRNAs in the hypoxia group were found compared to that in the normoxia group (fold change >1.5-fold and P < 0.05). The expression levels of circRNAs by qRT-PCR were consistent with those evaluated by microarray analysis. Gene ontology (GO) analysis showed that the putative function of their target genes for those differentially expressed circRNAs was primarily involved in cell development and its differentiation and regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway were the most significant. MAPK signaling pathway was found to be the core regulatory pathway triggered by hypoxia. CONCLUSIONS: The results indicate that the altered expression of specific circRNAs in MSCs is associated with hypoxic preconditioning. This finding provides further exploration of underlying mechanisms of the characteristic changes of MSCs with hypoxic preconditioning.

High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

Objective We aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke. Methods We retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed. Results Men had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome. Conclusions Our study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

Spinal primary central nervous system lymphoma: Case report and literature review.

Primary central nervous system lymphoma (PCNSL) is a very rare tumor of increasing incidence. It is often misdiagnosed due to the unspecific presentation or unavailable biopsy, and results in poor prognosis. PCNSL involved the spinal cord is extremely sparse. Here we report a gentleman presented with one-year history of progressive tremor in the left limbs and slight dysarthria as well as three-month history of paraparesis, tinnitus and insomnia. MR images disclosed the swollen cerebellum and cauda equine, with contrast enhancement in both meninges and nerve roots. The cerebrospinal fluid (CSF) revealed extremely high protein level. Tubercular meningitis was considered and anti-tuberculosis therapy was given for weeks but without relief. With progressive deterioration, the PCNSL was eventually presumed according to positive CSF cytology and exclusion of systemic involvement. However, the patient passed away within days. We then reviewed the current diagnostic methods of PCNSL. The biopsy, as the gold standard for PCNSL diagnosis, is not eligible for all patients suspected PCNSL. The presurgical diagnostic algorithm of PCNSL has been fixed by clinicians and we suggest the early and repeated CSF cytology should be included for definitive diagnosis.

Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation defects in zebrafish.

Moyamoya disease (MMD) is characterized by a stenosis at the terminal of the internal carotid artery and an abnormal vascular network at the base of the brain. RNF213 is a susceptibility gene for MMD in East Asians. The role of RNF213 in the etiology of MMD remains unknown. Here we generated rnf213a mutant zebrafish using transcription activator-like effector nuclease (TALEN) technique and described the characteristics of a zebrafish embryonic model of MMD. rnf213a mutant zebrafish developed abnormal angiogenesis in intersegmental vessels and cranial secondary vessels. Endothelial cells exhibited the defects in morphogenesis and formation of vascular tubes despite normal cell to cell contacts under electron microscope. Circulatory disorder was induced by abnormal sprouts in the trunk and head. Reduced circulation in the abnormal vessels was revealed by microangiography. No blood flow permeated across the vessels wall despite the extremely abnormal structure. rnf213a mutant showed lower erythrocyte velocity in dorsal aorta than that in wild-type siblings. In this study, we provided a promising in vivo model for MMD, and this model would aid to understand the function of rnf213a in angiogenesis.

The association between the ring finger protein 213 (RNF213) polymorphisms and moyamoya disease susceptibility: a meta-analysis based on case-control studies.

A number of studies assessed the association of ring finger protein 213 (RNF213) gene polymorphisms with moyamoya disease (MMD), but the results were not entirely consistent. This meta-analysis was performed to explore the relationship between RNF213 polymorphisms and moyamoya disease in Asian population. A systematic search from the PubMed, MEDLINE, EMBASE, ISI web of science, CNKI, China CBM and WANFANG DATA databases was conducted to retrieve published studies until March 2015. Statistical analyses were performed using the STATA12.0 software. Fixed or random effects model, subgroup analysis, sensitivity analysis, and publication bias were used to improve the comprehensive analysis. Eight papers including 904 MMD patients and 2258 controls were recruited in the meta-analysis. rs112735431 was closely associated with the risk of MMD among Asian population in all genetic models (dominant model: OR 103.39, 95 % CI 52.25-204.55, P = 1.69e-40; recessive model: OR 16.45, 95 % CI 6.00-45.10, P = 5.33e-08; additive model: OR 61.49, 95 % CI 22.07-171.33, P = 3.32e-15), especially in the Japanese population. Subgroup analysis revealed highly statistically significant higher risk in the patients with family histories. Although another polymorphism rs148731719 showed no significant association with the MMD, rs138130613 was found to be related to the higher risk in Chinese population (dominant model: OR 8.34, 95 % CI 1.72-40.47, P = 0.008). Our meta-analysis strengthens RNF213 rs112735431 is closely associated with the increased risk of MMD in Japanese, and the screening combined with rs112735431 and rs138130613may improve the detection rate for MMD in China.

Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population.

Ischemic stroke (IS) is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR) C677T, beta fibrinogen (FGB, ß-FG) A455G and T148C, apolipoprotein E (APOE) ε2-4, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and endothelial nitric oxide synthase (eNOS) G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and ß-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + ß-FG 148CC, ACE DD + ß-FG 148CT, and ACE ID + ß-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus) using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22-2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08-2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43-2.91, P < 0.001). The results of this study indicate that the ACE I/D and ß-FG T148C combination may result in significantly higher risk of IS in this Chinese population.

Variant rs1906591 on chromosome 4q25 confers increased risk of cardioembolic stroke in Chinese patients.

Ischemic stroke (IS) is a heterogeneous multifactorial disorder caused by both genetic and environmental factors. A genome-wide association study on stroke in Caucasians identified a variant on chromosome 4q25 that is significantly associated with IS, with the strongest risk for cardioembolic stroke (CES). The current study aims to investigate the association of the rs1906591 variant on 4q25 with IS through a case-control study in a Chinese Han population. A total of 712 IS patients and 774 control subjects were involved in the current research. Stroke subtyping was performed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The genotypes were determined using the SNaPshot technique. The association of the genotypes with the risk of IS was estimated using logistic regression analysis. The rs1906591 single nucleotide polymorphism variant was associated with the CES subtype in both recessive and additive models (recessive model: odds ratio [OR]=2.58, 95% confidence interval [CI] 1.47-4.53, p=0.001, adjusted OR=2.71, 95% CI 1.48-4.96, p=0.001; additive model: OR=2.50, 95% CI 1.19-5.25, p=0.015, adjusted OR=2.83, 95% CI 1.24-6.50, p=0.013). This result indicates that patients with the AA genotype have a higher rate of CES than other genotypes. However, the rs1906591 variant was not significantly associated with the overall incidence of stroke or other stroke subtypes. The rs1906591 variant is significantly associated with CES in the Chinese Han population, but not with other stroke subtypes.

The single nucleotide polymorphism rs2208454 confers an increased risk for ischemic stroke: a case-control study.

AIM: A recent genome-wide association study identified a strong association of covert magnetic resonance imaging infarcts with the single nucleotide polymorphism (SNP) rs2208454. The aim of this study was to determine whether the rs2208454 polymorphism is associated with an increased risk for ischemic stroke (IS). METHODS: Ischemic stroke patients (n = 712) and control subjects (n = 774) from a southern Chinese Han population were included. The snapshot technique was used for genotype analysis. RESULTS: Compared with the GT+GG or GG genotype, the frequency of the TT genotype was significantly higher in IS than in controls. After adjusting for age, gender, family history of IS, hypertension history, and history of diabetes mellitus, a significant correlation between the TT genotype and IS persisted (TT vs. GT+GG: adjusted OR = 1.79, 95% CI: 1.16-2.77; TT vs. GG: adjusted OR = 1.88, 95% CI: 1.20-2.94). In subgroup analyses, SNP rs2208454 was significantly associated with large artery atherosclerosis (LAA) (TT vs. GG: adjusted OR = 2.16, 95% CI: 1.19-3.93), but failed to show significant association with small-artery occlusion or cardioembolism IS subtypes. CONCLUSIONS: Single nucleotide polymorphism rs2208454 confers an increased risk for IS in a southern Chinese Han population. When the IS subtype was examined, the effect of the SNP was restricted to LAA.