Predisposing roles of paraoxonase-1 genetic variants in Korean ischemic stroke patients

Purpose: Statins (HMG-coA reductase inhibitors) protect vessels from atherosclerosis through various mechanisms, but the clinical significance of statin-induced high-density lipoprotein cholesterol (HDL) changes has not been established. We evaluated the effects of statin treatment on the antioxidative activities of HDLs in ischemic stroke patients with and without white matter hyperintensity (WMH). Methods: From January to December in 2013, eighty-two ischemic stroke patients (57 men, 25 women; mean age 67.0 ± 11.8 years) at the Wonkwang Medical Center were recruited retrospectively and antioxidant activity was assessed via paraoxonase 1 (PON1) activity. We studied changes in the patients’ lipid profiles and assessed PON1 activity in patients with and without WMH, at baseline and 8 weeks after treatment with rosuvastatin 10 mg/d. Results: All patients evaluated antioxidant activity using PON1 activity at admission. After 8 weeks of rosuvastatin treatment, the mean HDL concentration increased to 0.83± 10.1 mg/dL. The HDL levels increased in 54 patients (64.3%) and decreased in 30 patients (35.7%). PON1 activity increased to 15.0% in all patients, regardLess of WMH after rosuvastatin treatment (+ 25.4% in subjects without WMH; P < 0.001). Baseline PON1 activity modestly correlated with HDL levels (r = 0.365, P = 0.019); however, PON1 activity after treatment did not correlate with HDL levels (r = 0.149, P = 0.347). Conclusion: Our findings suggest that statins increase antioxidant activity, especially assessed via PON1 activity, in ischemic stroke patients who did not have WMH.

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Association of the APOE, MTHFR and ACE genes polymorphisms and stroke in Zambian patients

Neurology International ◽

10.4081/ni.2013.e20 ◽

2013 ◽

Vol 5 (4) ◽

pp. 20 ◽

Cited By ~ 13

Author(s):

Masharip Atadzhanov ◽

Mwila H. Mwaba ◽

Patrice N. Mukomena ◽

Shabir Lakhi ◽

Sruti Rayaprolu ◽

...

Keyword(s):

Genetic Variation ◽

Ischemic Stroke ◽

Genetic Variants ◽

Hemorrhagic Stroke ◽

The Other ◽

Stroke Patients ◽

Stroke Subtype ◽

Increased Risk ◽

Apoe Locus ◽

The Difference

The aim of the present study was to investigate the association of APOE, MTHFR and ACE polymorphisms with stroke in the Zambian population. We analyzed 41 stroke patients and 116 control subjects all of Zambian origin for associations between the genotype of the APOE, MTHFR and ACE polymorphisms and stroke. The APOE ε2ε4 genotype showed increased risk for hemorrhagic stroke (P<0.05) and also a high risk for ischemic stroke (P=0.05). There was complete absence of the APOE ε2ε2 and the MTHFR TT genotypes in the Zambian population. The difference between cases and controls was not significant for the other genetic variants when analyzed for relationship between stroke, stroke subtype and genotype. We show that genetic variation at the APOE locus affects susceptibility to stroke. No detectable association were observed for the MTHFR and ACE genotypes and stroke in the Zambian population.

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Abstract TP216: Identifying Common Genetic Variants Associated With Fatal Stroke in Incident Ischemic Stroke Patients

Stroke ◽

10.1161/str.51.suppl_1.tp216 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Vida Abedi ◽

Jiang Li ◽

Ayesha Khan ◽

Aniket Mishra ◽

Stéphanie Debette ◽

...

Keyword(s):

Ischemic Stroke ◽

Genetic Variants ◽

Genetic Risk ◽

Sodium Current ◽

Unmet Need ◽

Case Control ◽

Large Artery ◽

Stroke Patients ◽

Fatal Stroke ◽

Common Genetic Variants

Introduction: There is an unmet need to understand the genetic factors associated with stroke outcome. The purpose of this study is to identify the common genetic variants, if any, associated with incident of ischemic stroke in a community-based population and to determine if any genetic risk can be enriched in fatal stroke patients. Methods: Cases and controls of ischemic stroke were identified by leveraging the comprehensive Electronic Health Record, and endophenotypes, e.g. the fatal or nonfatal stroke was defined by those dying within one month (fatal incidence) or surviving to 12 months (nonfatal incidence) of their first-ever stroke incident. The GWAS was carried out in a nested case-control design by considering all patients with age >79 and without any stroke-related diagnostic codes as low-risk control. A linear mixed regression model (SAIGE) with saddlepoint approximation, adjusted for covariates was conducted to account for the relatedness and case-control imbalance. Results: No genome-wide significant association was identified for ischemic stroke (n=1,179) versus control (n=7,489). When stratifying stroke patients by the fatality (n=61/1,118), rs80094021 (MAF = 0.038; OR=3.332±0.635; p=9.04E-11) and SNPs in LD with, located at an intronic region of TIAM1, were the top associated signal. All these SNPs served as eQTL for TIAM1(β=0.144, p=5.8E-13, eQTLGen). Rs79694970, the second top SNP (MAF = 0.020; OR=4.179±0.931; p=9.27E-09), is located near GPD1L and functions as eQTL for GPD1L(β=-0.279, p=6.1E-28). GPD1L plays a role in the DPD1L-dependent SCN5A phosphorylation pathway, thereby regulating cardiac sodium current. Dysfunction of sodium current can cause fatal ventricular arrhythmia. According to PheWAS data from UK Biobank, rs80094021 showed a moderate association with high cholesterol (p=0.0045), coronary atherosclerosis (p=0.0075), and angina (p=0.012), with the same direction for the minor allele which increased the risk for fatal stroke. rs79694970 were associated with ischemic stroke (large artery atherosclerosis) with p=0.0016. Conclusion: Through stratification of ischemic stroke by fatality some genetic risk factors and genes with biological relevant to the pathogenesis of stroke could be identified.

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