Dataset Information

Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke.

ABSTRACT: Objective: Cystatin C, a marker of atherosclerosis, is encoded by CST3. We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of CST3 are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis. Methods: This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of CST3 were selected based on the strong association with cystatin C concentration. Results: Two loci of CST3 (rs13038305 and rs911119) were analyzed in 3,833 ischemic stroke patients. Carriers of T allele in rs13038305 and C allele in rs911119 tend to have lower serum cystatin C levels (p < 0.05). Compared with C/C as a reference in rs13038305, odds ratio (OR) of T/T was 0.486, 95% CI 0.237-0.994, p = 0.048. Per C allele of rs13038305 also showed an increased level of low-density lipoprotein cholesterol (LDL-C), β (95% CI) was 1.335 (1.008-1.250), p = 0.044. No correlation was found between the selected SNPs and stroke prognosis (functional outcome, recurrence, and mortality). Conclusions: Carriers of the T allele in rs13038305 tend to have a lower proportion of LAAS. rs13038305 and rs911119 polymorphisms were likely to affect cystatin C concentration independently of kidney function.

SUBMITTER: Ding Y

PROVIDER: S-EPMC8548665 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke.

Ding Yarong Y Xu Zhe Z Pan Yuesong Y Meng Xia X Xiang Xianglong X Li Hao H Liu Liping L Wang Yongjun Y

Frontiers in neurology 20211013

Objective: Cystatin C, a marker of atherosclerosis, is encoded by CST3. We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of CST3 are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis. Methods: This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of CST3 were selected b ...[more]

PMID: 34721268

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Project description:ObjectiveTo investigate the association of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, osteoprotegerin (OPG) and death receptor 5 (DR5) with large-artery atherosclerosis (LAA) stroke and its prognosis.MethodsWe included patients with LAA stroke (n = 132) according to the TOAST classification system and controls (n = 60). To evaluate the extent and severity of cerebral atherosclerosis, the LAA stroke group was subdivided into 3 subgroups by number of cerebral arteries with atherosclerotic stenosis (≥50%): single, double and multiple (≥3). Plasma levels of TRAIL, OPG and DR5 were measured by ELISA. Ordinal logistic regression was used to analyze the association between the plasma levels of TRAIL, OPG, DR5 and the severity of cerebral atherosclerosis. Prognosis was determined by the Modified Rankin Scale at 3 months after stroke. Receiver operating characteristic (ROC) curve was used to evaluated TRAIL as a predictor of prognosis.ResultsPlasma TRAIL level was significantly lower for LAA patients than controls (P<0.001), while plasma OPG and DR5 levels were higher (both P<0.001). Logistic regression analysis revealed that risk of severe cerebral atherosclerosis was reduced significantly with increased plasma level of TRAIL (OR 0.438; 95% CI 0.282-0.681; P<0.001), whereas increased with high plasma levels of OPG and DR5 (OR 2.707; 95% CI 1.702-4.302, P <0.001; OR 3.593; 95% CI 1.878-6.869, P <0.001). Plasma TRAIL level was negatively correlated with the prognosis (r = - 0.372, P <0.001). The optimal cut-off value of TRAIL for prognosis was 848.63 pg/mL. The sensitivity and specificity at this cut-off value were 63.1% and 86.2%, respectively. After adding the plasma TRAIL level into the multivariate model of ROC, the area under the ROC curve was increased from 0.639 to 0.785, but the change was not statistical significant (P = 0.146).ConclusionsTRAIL and its receptors OPG and DR5 may be involved in LAA stroke and the plasma level of TRAIL may be a biomarker predicting the severity of cerebral atherosclerosis and the prognosis of LAA stroke.

Project description:Objectives The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410–9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420–7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017–2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021–2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.

Dataset Information

Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke.

Publications

Association Between <i>CST3</i> Gene Polymorphisms and Large-Artery Atherosclerotic Stroke.

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