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NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

ABSTRACT: Single-nucleotide polymorphisms (SNPs) play an important role in our susceptibility to disease, the severity of illness and the way our body responds to treatment. This study evaluated the impact of three polymorphisms on the susceptibility and functional outcome of ischemic stroke (IS). Three hundred and eight patients and 300 healthy volunteers were enrolled. Polymorphisms of NOX4 rs11018628, MTHFR rs1801133 and NEIL3 rs12645561 were detected in both groups. Smoking (P<0.001), drinking (P<0.001), hypertension (P<0.001) and diabetes (P=0.006), as traditional vascular risk factors for IS, were confirmed in our study. Logistic regression analyses with adjustment for age, sex, smoking, drinking, diabetes, hypertension and total cholesterol showed that the variant genotypes of NOX4 rs11018628 were associated with a significantly decreased risk (Dominant model: OR=0.32, 95% CI=0.22-0.48, P<0.001) and a better short-term recovery of IS (Dominant model: OR=0.57, 95% CI=0.35-0.95, P=0.029). This study demonstrates that the NOX4 rs11018628 SNP is associated with decreased risk in developing IS and better short-term recovery of patients. This suggests that the genetic variant of NOX4 rs11018628 may contribute to the etiology of IS.

SUBMITTER: He W

PROVIDER: S-EPMC6257675 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

He Wei W Wang Qingguang Q Gu Lujun L Zhong Lingling L Liu Dinghua D

Experimental and therapeutic medicine 20181017 6

Single-nucleotide polymorphisms (SNPs) play an important role in our susceptibility to disease, the severity of illness and the way our body responds to treatment. This study evaluated the impact of three polymorphisms on the susceptibility and functional outcome of ischemic stroke (IS). Three hundred and eight patients and 300 healthy volunteers were enrolled. Polymorphisms of NOX4 rs11018628, MTHFR rs1801133 and NEIL3 rs12645561 were detected in both groups. Smoking (P<0.0 ...[more]

PMID: 30542483

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Project description:BackgroundIntravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome.MethodsIn this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0-9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event.ResultsPoor outcomes were significantly more frequent in the CBS 0-9 group. Plasminogen activity on admission was significantly higher in the CBS 0-9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0-9) could be demonstrated (OR:0.519; 95%CI:0.298-0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated.ConclusionsCBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.

Project description:The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity.Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding).AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04).Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.

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NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

Publications

<i>NOX4</i> rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

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