Large Artery Atherosclerotic Stroke Patients Research Articles

Identification and characterization of extrachromosomal circular DNA in large-artery atherosclerotic stroke.

Extrachromosomal circular DNA (eccDNA) is a new biomarker and regulator of diseases. However, the role of eccDNAs in large-artery atherosclerotic (LAA) stroke remains unclear. Through high-throughput circle-sequencing technique, the length distribution, genomic characteristic and motifs feature of plasma eccDNA from healthy controls (CON) and patients with LAA stroke were analysed. Then, the potential functions of the annotated eccDNAs were investigated using GO and KEGG pathway analyses. EccDNAs mapped to the reference genome showed SHN3 and BCL6 were LAA stroke unique transcription factors. The genes of differentially expressed eccDNAs between LAA stroke patients and CON were mainly involved in axon/dendrite/neuron projection development and maintenance of cellular structure via Wnt, Rap1 and MAPK pathways. Moreover, LAA stroke unique eccDNA genes played a role in regulation of coagulation and fibrinolysis, and there were five LAA stroke unique eccDNAs (Chr2:12724406-12724784, Chr4:1867120-186272046, Chr4:186271494-186271696, Chr7:116560296-116560685 and Chr11:57611780-5761192). Additionally, POLR2C and AURKA carried by ecDNAs (eccDNA size >100 kb) of LAA stroke patients were significantly associated with development of LAA stroke. Our data firstly revealed the characteristics of eccDNA in LAA stroke and the functions of LAA stroke unique eccDNAs and eccDNA genes, suggesting eccDNA is a novel biomarker and mechanism of LAA stroke.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP–SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49–0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Blood pressure variability and outcome in atherosclerosis versus cardioembolism cerebral large vessel occlusion after successful thrombectomy.

Higher blood pressure variability (BPV) has been proven associated with worse functional outcome after endovascular treatment (EVT). However, this association is not established according to different stroke etiologies. In this study, we compared patients with the two highest proportions of stroke etiologies-cardioembolism (CE) and large-artery atherosclerosis (LAA), aiming to explore appropriate strategies of BP management for different etiologies. We enrolled patients with large vessel occlusion (LVO) in anterior circulation who underwent EVT and achieved successful recanalization retrospectively. 24-h blood pressure (BP) and BPV measured as blood pressure reduction (BPr), standard deviation (SD), coefficient of variation (CV), successive variation (SV), average real variability (ARV) after EVT were collected for systolic blood pressure (SBP) and diastolic blood pressure (DBP). The favorable outcome was defined as functional independence by 90-day modified Rankin Scale (mRS 0-2). In our cohort, higher BPV parameters significantly resulted in 90d functional dependence in CE-LVO patients (SBPSV OR: 1.083, 95%CI = 1.009-1.163; SBPARV OR: 1.121, 95%CI = 1.019-1.233; DBPSD OR: 1.124, 95%CI = 1.007-1.1256; DBPCV OR: 1.078, 95%CI = 1.002-1.161). However, for LAA-LVO patients, no positive results correlated 90d functional dependence with 24-hour BPV. Additionally, 90d functional dependence in CE patients with poor collaterals were significantly dependent on post-procedural BPV (DBPmax OR: 1.044, 95%CI = 1.002-1.087; DBPSD OR: 1.229, 95%CI = 1.022-1.1.479; DBPCV OR: 1.143, 95%CI = 1.009-1.295). Whereas to patients with good collaterals, there did not exist such a correlation. In summary, stroke etiologies should probably be taken into consideration to optimize individualized BP management strategies. In order to achieve better clinical outcomes for patients with acute ischemic stroke due to large vessel occlusion, stricter blood pressure management should be taken in cardioembolic stroke patients in contrast with large artery atherosclerotic stroke patients after successful endovascular therapy.

SERPINA1 gene expression in whole blood links the rs6647 variant G allele to an increased risk of large artery atherosclerotic stroke.

The rs6647 variant G allele in SERPINA1 gene was reported to be associated with the risk of large artery atherosclerotic stroke (LAS), however, the mechanism remains unclear. Here, we performed a functional annotation of the rs6647 variant by using the software HaploReg version 4.1 (HaploReg v4.1). Next, the expression quantitative trait loci (eQTLs) analysis of multiple datasets was conducted for determining the association between the rs6647 and SERPINA1 expression in various tissues. Then, a case-control gene expression analysis was done using two independent ischemic stroke (IS) gene expression datasets. Finally, SERPINA1 expression in whole blood samples from 8 LAS patients and 14 healthy persons were compared. The functional annotation suggested that the rs6647 regulates gene expression in multiple human tissues especially in brain and blood. The eQTLs analysis revealed a significant association of the rs6647 G allele with increased expression of SERPINA1 gene only in whole blood. Compared with the controls, there was an increased expression of SERPINA1 gene in whole blood in both IS patients and LAS patients. SERPINA1 gene expression in whole blood bridges the rs6647 variant G allele with increased LAS risk, providing new insights into the mechanisms underlying role of the rs6647 in determining LAS risk.

Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.

Collateral density variations are a major determinant of stroke outcome. Here, we explored the association of missense variants in hypoxia-induced VEGFA/VEGFR2 signaling and stroke outcome. We recruited 683 large artery atherosclerotic (LAA) stroke patients as the training set from Nanjing Stroke Registry Program between August 2013 and January 2016. To validate the findings from the training set, we recruited an additional 333 LAA stroke patients between February 2016 and January 2017 as the validation set. Genotyping of target SNPs (rs11549465 [HIF-1α], rs11549467 [HIF-1α], rs1870377 [VEGFR2], and rs2305948 [VEGFR2]) was conducted using a SNPscan method. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score > 2 at three months after index event. In the training set, the AA genotype of rs1870377 led to a decreased risk of unfavorable outcomes in the recessive model (AA vs. TA + TT, OR 0.60, 95% CI 0.38-0.95, P = 0.031). This was confirmed in the validation set (OR 0.43, 95% CI 0.21-0.86, P = 0.017) and the combined set (OR 0.54, 95% CI 0.36-0.79, P = 0.002). We also found that A allele was a protective factor for stroke outcome in both validation set and combined set (OR 0.70, 95% CI 0.49-0.99, P = 0.044 and OR 0.77, 95% CI 0.63-0.94, P = 0.012, respectively). In silico analysis indicated that the rs1870377 variant led to structural alterations in VEGFR2 that may influence its activity. Our findings demonstrate that the rs1870377 in the hypoxia-induced VEGFA/VEGFR2 axis predicts the 3-month outcome of patients with LAA stroke.

Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping.

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550-0.907; P = 0.006). The analysis of SNP-SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

Associations between GUCY1A3 genetic polymorphisms and large artery atherosclerotic stroke risk in Chinese Han population: a case-control study

BackgroundPrevious genome-wide association studies have found two single nucleotide polymorphisms (SNP) rs7692387 and rs1842896 located on or near the GUCY1A3 gene were associated with coronary artery disease (CAD). GUCY1A3 was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of the GUCY1A3 and large artery atherosclerotic (LAA) stroke. This study aimed to investigate the associations between the GUCY1A3 rs7692387, rs1842896 polymorphisms and LAA stroke susceptibility.MethodsA total of 298 LAA stroke patients and 300 control subjects from a southern Chinese Han population were included. SNaPshot technique was used for genotype analysis. Associations between genotypes and LAA stroke susceptibility were analyzed with logistic regression model.ResultsOur study found that under the recessive model (TT vs. GT + GG), the GUCY1A3 rs1842896 polymorphism was significantly correlated with LAA stroke (OR = 1.48, 95%CI: 1.07–2.04, P = 0.018). After adjustment for its effects on age, gender, cigarette smoking, total cholesterol, low-density lipoprotein cholesterol, HbA1c, hypertension, diabetes mellitus, and CAD, the rs1842896 TT genotype retained association with increased susceptibility to LAA stroke (recessive model: adjusted OR = 1.96, 95%CI: 1.22–3.17, P = 0.006). However, association between rs7692387 polymorphism with LAA stroke was not observed.ConclusionOur results indicate that the GUCY1A3 rs1842896 polymorphism is an LAA stroke risk factor in Southern Han Chinese.

PTPN22 Gene Polymorphisms Are Associated with Susceptibility to Large Artery Atherosclerotic Stroke and Microembolic Signals

Large artery atherosclerotic stroke (LAAS) is the most common ischemic stroke (IS) subtype, and microemboli may be clinically important for indicating increased risk of IS. The inflammatory process of atherosclerosis is well known, and lymphoid phosphatase (Lyp), which is encoded by the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene, plays an important role in the inflammatory response. Our study was intended to evaluate the relationship between PTPN22 gene and LAAS and microembolic signals (MES). Three loci of the PTPN22 gene (rs2476599, rs1217414, and rs2488457) were analyzed in 364 LAAS patients and 369 control subjects. A genotyping determination was performed using the TaqMan assay. The G allele of rs2488457 might be related to a higher risk for developing LAAS and MES (odds ratio (OR) = 1.456, 95% confidence interval (CI) 1.156-1.833, P = 0.001; OR = 1.652, 95% CI 1.177-2.319, P = 0.004, respectively). In the LAAS group, the prevalence of the GTG haplotype was higher (P < 0.001) and the prevalence of the GCC haplotype was lower (P = 0.001). An interaction analysis of rs2488457 with smoking showed that smokers with the CG/GG genotypes had a higher risk of LAAS, compared to nonsmokers with the rs2488457 CC genotype (OR = 2.492, 95% CI 1.510–4.114, P < 0.001). Our research indicated that the PTPN22 rs2488457 might be related to the occurrence of LAAS and MES in the Han Chinese population. In addition, the rs2488457 polymorphism and the environmental factor of smoking jointly influenced the susceptibility of LAAS.

Fasting apolipoprotein B48 is associated with large artery atherosclerotic stroke: a case-control study

Fasting Apolipoprotein B48 (ApoB48) is reported to be a well surrogate marker for postprandial lipidemia and have been repeatedly associated with cardiovascular disease. However, whether ApoB48 is also a risk factor for ischemic stroke have not been reported. In this study, our object is to explore the relationship between fasting plasma ApoB48 levels and the large artery atherosclerotic (LAA) stroke.A 1:1 age-(±2), gender-matched case-control study was conducted. LAA patients and healthy controls admitted to our center were prospectively recruited. Clinical data were collected and enzyme-linked immunosorbent assay (ELISA) was used to measure the fasting plasma ApoB48 levels.A cohort of 234 LAA stroke patients and 234 controls were enrolled. Fasting plasma ApoB48 levels were significantly higher in LAA stroke patients than in controls (4.76(3.46) vs 4.00(2.4), P < 0.001). Conditional multivariable analyses indicated that fasting ApoB48 levels were associated with LAA stroke (odds ratio: 1.18; 95% confidence interval: 1.04–1.35; P = 0.014).Our study indicates that increased fasting plasma ApoB48 may be a risk factor for LAA stroke.

Chromosome 10q25 polymorphism is associated with susceptibility to large artery atherosclerotic stroke

Background and aimsA recent genome-wide association study (GWAS) reported an association between a single nucleotide polymorphism (SNP) rs11196288 and risk of early-onset large artery atherosclerotic (LAA) stroke in European population. The interaction between genetic and environmental factors such as age has also received increasing attention. We performed this study to investigate the association between the rs11196288A > G polymorphism and LAA stroke risk in the Chinese Han population and test whether age interacts rs11196288 to influence LAA stroke risk. MethodsGenotyping of rs11196288 was performed in 1066 LAA stroke patients and 1167 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs11196288A > G polymorphism on susceptibility and short-term outcome of LAA stroke. Nomograms were performed to estimate probability of risk for an individual patient. ResultsA significant decrement of LAA stroke risk was found in co-dominant (AG vs. AA, OR = 0.76, 95% CI = 0.64–0.91, P = 0.003; GG vs. AA, OR = 0.65, 95% CI = 0.50–0.85, P = 0.002), dominant (AG/GG vs. AA, OR = 0.74, 95% CI = 0.62–0.87, P < 0.001) and recessive models (GG vs. AA/AG, OR = 0.76, 95% CI = 0.59–0.97, P = 0.028) of rs11196288. However, the interaction between age and genotypes of rs11196288 was not statistically significant, and no significant association was observed between the rs11196288A > G polymorphism and short-term outcome of LAA stroke (P > 0.05). ConclusionsIn the southeastern Chinese population, the rs11196288A > G polymorphism is associated with decreased risk of LAA stroke.

HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population.

Recently, a genome-wide association study (GWAS) detected two histone deacetylase 9 (HDAC9) polymorphisms (rs2074633 and rs28688791) which may be associated with risk of large artery atherosclerotic (LAA) stroke. This study aimed to investigate whether these two polymorphisms were associated with susceptibility, severity, and short-term outcome of LAA stroke in a southern Chinese Han population. rs2074633 and rs28688791 were genotyped using SNPscan technology in 1011 LAA stroke patients and 1121 healthy controls. Stroke severity on admission and short-term outcome were, respectively, assessed by the National Institute of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale score at 3months after stroke onset. rs2074633 (P = 0.039) and rs28688791 (P = 0.025) were associated with risk of LAA stroke. In subgroup analysis according to sex and age, this increased risk was only found in males (P = 0.029 for rs2074633; P = 0.013 for rs28688791) and adults aged < 60years (P = 0.009 for rs2074633; P = 0.003 for rs28688791). Moreover, we detected significant interactions between these two polymorphisms and age (Pinteraction = 0.027 for rs2074633; Pinteraction = 0.044 for rs28688791). The CC genotype of rs28688791 (P = 0.037) was also associated with moderate and severe stroke (NIHSS ≥ 6). Additionally, the CC genotype of rs2074633 and rs28688791 (rs2074633, P = 0.019; rs28688791, P = 0.023) showed significant association with unfavorable short-term outcome of LAA stroke. Our results indicated that HDAC9 polymorphisms may be used as biomarkers for susceptibility, severity, and short-term outcome of LAA stroke.

Association of SNPs in the TIMP-2 gene and large artery atherosclerotic stroke in southern Chinese Han population.

Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) regulates the extracellular matrix degradation, which involved in vascular remodeling and dysfunction, destabilization of atherosclerotic plaque and many other pathological processes. The rupture of atherosclerotic plaque is the trigger of Large artery atherosclerotic (LAA) stroke. We speculate that the Single nucleotide polymorphisms (SNPs) in TIMP-2 may have an association with LAA stroke. To prove this hypothesis, we conducted this case-control study. 250 LAA stroke patients and 250 healthy controls were collected for the analysis of TIMP-2 polymorphisms. Among six SNPs, we detected no deviation from Hardy-Weinberg equilibrium in control group. There was a significant difference in rs4789936 T allele frequency between patient and control groups (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009), which means lower risk of LAA stroke. We observed the rs4789936 had a decreased risk of LAA stroke according to the codominant (OR = 0.64, 95% CI = 0.44–0.92, P = 0.026), dominant (OR = 0.62, 95% CI = 0.43-0.88, P = 0.008), overdominant (OR = 0.68, 95% CI = 0.48–0.98, P = 0.039), log-additive (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009) models analyses. However, these findings could only validate under dominant model (OR = 0.65, 95% CI = 0.42–1.00, P = 0.049) after adjustment of gender and age. The results indicate a potential association between TIMP-2 variants and LAA stroke risk in southern Chinese Han population.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel biomarker for large-artery atherosclerotic stroke

ABSTRACTBackground: Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown associated with the progression of atherosclerosis in endothelial cells. We sought to assess whether the baseline serum sLOX-1 levels are correlated with the presence and short-term functional outcome of large-artery atherosclerotic (LAA) stroke. Methods: The study recruited 241 subjects, including 148 consecutive patients with acute ischemic stroke with the subtype of LAA and 93 non-stroke controls. Clinical and laboratory data, including serum concentration of sLOX-1, were collected within 24 h of admission, and the severity of LAA stroke patients was evaluated by National Institutes of Health Stroke Scale score. And functional outcome was assessed by modified Rankin Scale three months after stroke. The association between sLOX-1 level and the functional outcome at three months was analyzed by multiple logistic regression models. Results: Serum levels of sLOX-1 in the LAA stroke patients were significantly higher as compared to normal controls (2.48 ± 0.93 ng/ml vs. 2.22 ± 0.79 ng/ml in the controls, t = 2.301, p = 0.022). The levels of serum sLOX-1 in patients with good outcome were significantly lower than those with poor outcome (2.39 ± 0.94 ng/ml vs. 2.77 ± 0.84 ng/ml, p = 0.032). After adjusting for potential confounders, sLOX-1 was still an independent predictor for the function outcome with an adjusted OR of 3.39 (95% CI, 1.61–7.11, p = 0.001). Conclusions: The serum sLOX-1 level was higher in patients with LAA stroke, and it was an independent predictor of functional outcome in patients with LAA ischemic stroke.

Angiopoietin-like protein 4 serum levels and gene polymorphisms are associated with large artery atherosclerotic stroke

BackgroundAngiopoietin-like protein 4 (ANGPTL4) is a central player in lipid metabolism and atherosclerosis and may thus be involved in ischaemic stroke. However, no study in humans has investigated the association of ANGPTL4 gene polymorphisms or serum levels with ischaemic stroke. MethodsWe investigated the influence of the tagged single nucleotide polymorphisms (tSNPs) rs4076317 (c.207C>G) and rs1044250 (c.797C>T; T266M) of the ANGPTL4 gene on ischaemic stroke risk in a large group of 712 large artery atherosclerotic (LAA) stroke patients and 828 controls. In addition, we examined the association of the serum ANGPTL4 levels with lipid metabolism, LAA stroke severity and ischaemic volume in a sample of 302 LAA stroke patients and 307 controls. ResultsThe findings reveal that rs4076317 exerts a co-dominant effect on lower serum TG levels compared with common homozygotes. Fewer stroke cases were homozygous for variants of rs4076317 compared with the controls (7.0% vs. 10.9%). The serum ANGPTL4 levels in patients were significantly higher than those in the controls in a univariate manner (P=0.001) and after adjustment for other risk factors (1.463 [1.215–1.835]; P<0.001). Consistently, the ANGPTL4 levels were statistically correlated with higher NIHSS scores (r=0.172, P=0.003) and larger lesion volumes (r=0.124, P=0.031). ConclusionWe concluded that the tagged SNPs and high serum levels of ANGPTL4 are associated with LAA stroke and the lipid characteristics.

Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population

Background: Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. Methods: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. Results: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)). Conclusion: Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke.

Abstract T P169: Acute Cardioembolic vs. Large Artery Atherosclerotic Infarction-related Lesion Topography and Right-Left Propensity: A Multi-center Quantitative Magnetic Resonance Imaging Study

Background and Purpose: A recent study showed that cardiogenic emboli might flow more frequently into the right hemisphere, whereas atheromatous aortic arch emboli might flow more frequently into the left hemisphere. We tried to 1) see if cardioembolic (CE) infarct volume would be larger in the right hemisphere than in the left hemisphere, and 2) depict anatomical regions showing CE vs. large artery atherosclerotic (LAA) infarction-related right-left propensity. Methods: In this study on carotid artery territory CE (n = 694) vs. LAA (n = 1162) acute ischemic stroke patients who were enrolled consecutively from 11 nationwide stroke centers, we quantitatively registered diffusion magnetic resonance imaging lesions onto the Montreal Neurologic Institute brain template. Results: In patients with bilateral CE stroke (n = 163), right hemispheric infarct size was about two times bigger than the contralateral left hemispheric infarct size (p = 0.002). However, in patients with either unilateral (n = 925) or bilateral (n = 184) LAA stroke, there was no significant difference in the right vs. left hemispheric infarct size between the right vs. left unilateral infarct groups or within the bilateral infarct group (all p &gt; 0.05). In patients with unilateral CE stroke (n = 510), there was no significant difference in the infarct size between the groups with right vs. left hemispheric lesions. Age and infarct volume-adjusted p-value maps of the CE vs. LAA stroke patients, which were corrected for multiple comparisons, revealed the brain regions with a significantly higher infarct frequency in CE stroke than in LAA stroke. The significant clusters were observed only in the right hemisphere, encompassing both the superior and inferior division middle cerebral artery territories, particularly in the pial and corticosubcortical regions including the claustrum and insula. Conclusion: The present multi-center quantitative magnetic resonance imaging study confirms the ‘right &gt; left’ propensity of CE (vs. LAA) stroke.

Polymorphisms of DNA Repair Pathway Genes and Cigarette Smoking in Relation to Susceptibility to Large Artery Atherosclerotic Stroke among Ethnic Chinese in Taiwan

Cigarette-smoking induced oxidative DNA damage to endothelial cells has been reported to play an etiological role in atherosclerosis development. Individual vulnerability to oxidative stress through smoking exposure and the ability to repair DNA damage, which plays a critical role in modifying the risk susceptibility of large artery atherosclerotic (LAA) stroke, is hypothesized. Thus, we examined the effect of genetic polymorphisms of DNA repair pathway genes and cigarette smoking in relation to risk susceptibility of LAA stroke. We enrolled 116 LAA stroke patients and 315 healthy controls from the Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan. Genotyping of polymorphisms of the OGG1 (Ser326Cys), XRCC1 (Arg399Gln), ERCC2 (Lys751Gln), and ERCC5 (Asp1104His) genes was performed and used to evaluate LAA stroke susceptibility. Of those non-synonymous polymorphisms, the ERCC2 Lys751Gln variant was found to be associated with LAA stroke risk (OR: 1.69, 95%CI: 1.02-2.86), and this association was more pronounced in smokers, manifesting a 2.73-fold increased risk of LAA stroke (p=0.027). A joint effect on risk elevation of LAA stroke was seen in those patients with OGG1 and ERCC2 polymorphisms (OR: 2.75, 95%CI: 1.26-6.00). Moreover, among smokers carrying the OGG1 Ser326Cys polymorphism, there was a tendency toward an increased risk of LAA stroke in those patients who had a greater number of high-risk genotypes of XRCC1, ERCC2, and ERCC5 polymorphisms (p(trend)=0.010). The susceptible polymorphisms of DNA repair pathway genes may have a modifying effect on the elevated risk of LAA stroke in smokers among ethnic Chinese in Taiwan.