Highlights
- •A cross-sectional study in consecutive survivors of their first ischemic stroke and population controls was performed.
- •Stroke subtype was categorized using the validated Causative Classification of Stroke System.
- •An association between rs1799963A allele and undetermined stroke was found.
- •A strong interaction between smoking and a copy of rs1799963A allele was reported.
Abstract
Objective
Due to contradictory results of previous studies evaluating the association between
ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS
patients, particularly those older than 60 years, is not recommended. We evaluated
the differences in the distribution of rs6025 and rs1799963 polymorphisms according
to IS subtypes and their interaction with smoking.
Methods
We conducted a case–control study of 423 hospital-based consecutive survivors of their
first-ever IS and 614 population-based controls. Survivors (18–81 years) with IS documented
by brain imagining were examined at a median of 16 months after the index event. The
stroke subtype was categorized using the Causative Classification of Stroke System.
Controls (50–75 years) were free of a history of stroke/TIA, coronary heart disease,
and venous thromboembolism.
Results
Age- and gender-adjusted prevalence of individuals carrying at least one copy of the
rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large
artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion,
and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate
adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR:
3.67; 95% CI: 1.52–8.85; p = 0.004). There was strong evidence of rs1799963 × smoking
synergistic interaction (OR: 5.14; 95% CI: 1.65–16.01; p = 0.005). There was no association
of rs6025 with IS in general, or with any subtype.
Conclusions
In our consecutive IS survivors, carriage of the rs1799963A allele is associated with
undetermined stroke. This effect appears to be confined to smokers.
Keywords
Abbreviations:
BMI (body mass index), eGFR (estimated glomerular filtration rate), IS (ischemic stroke), PFO (patent foramen ovale), SSS-TOAST (Trial Org 10172 in Acute Stroke Treatment), EQA (external quality assessment), IQC (internal quality control)To read this article in full you will need to make a payment
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References
- Genetic susceptibility to venous thrombosis.NEJM. 2001; 344: 1222-1231
- Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls.Arch. Neurol. 2004; 61: 1652-1661
- Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies.AHJ. 2003; 146: 948-957
- Testing for inherited thrombophilias in arterial stroke: can it cause more harm than good?.Stroke. 2010; 41: 2985-2990
- Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.Stroke. 2014; 45: 961-967
- A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System.Stroke. 2007; 38: 2979-2984
- Ischemic stroke subtypes and thrombophilia in young and elderly Brazilian stroke patients admitted to a rehabilitation hospital.Stroke. 2005; 36: 2012-2014
- Inherited thrombophilia in ischemic stroke and its pathogenic subtypes.Stroke. 2001; 32: 1793-1799
- G1691A factor V and G20210A FII mutations, acute ischemic stroke of unknown cause, and patent foramen ovale.Thromb. Res. 2012; 130: 720-724
- Prothrombotic gene variation in patients with large and small vessel disease.Neuroepidemiology. 2008; 31: 89-92
- Evaluation of the roles of the Leiden V mutation and ACE I/D polymorphism in subtypes of ischaemic stroke.J. Neurol. 2001; 248: 756-761
- The factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT and platelet glycoprotein IIIa 1565TC mutations in patients with acute ischemic stroke and atrial fibrillation.Stroke. 2007; 38: 1069-1071
- Common genetic coagulation variants are not associated with ischemic stroke in a case-control study.Neurol. Res. 2010; 32: 519-522
- Large artery stiffness and carotid flow pulsatility in stroke survivors.J. Hypertens. 2014; 32: 1097-1103
- Experience from a multicentre stroke register: a preliminary report.Bull. World Health Organ. 1976; 54: 541-553
- Longitudinal trends in cardiovascular mortality and blood pressure levels, prevalence, awareness, treatment, and control of hypertension in the Czech population from 1985 to 2007/2008.J. Hypertens. 2010; 28: 2196-2203
- 2007 guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the european society of hypertension (ESH) and of the european society of cardiology (ESC).J. Hypertens. 2007; 25: 1105-1187
- Longitudinal trends in major cardiovascular risk factors in the Czech population between 1985 and 2007/8. Czech MONICA and Czech post-MONICA.Atherosclerosis. 2010; 211: 676-681
- Levey AS and Stevens PE. The Kidney Disease Improving Global Outcomes (KDIGO) guideline update for chronic kidney disease: evolution not revolution.Clin. Chem. 2013; 59: 462-465
- The frequencies of six important thrombophilic mutations in a population of the Czech Republic.Physiol. Res. 2014; 63: 245-253
- 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).J. Hypertens. 2013; 31: 1281-1357
- Global guideline for type 2 diabetes.Diabetes Res. Clin. Pract. 2014; 104: 1-52
- Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio.JASN. 1996; 7: 930-937
- A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.Blood. 1996; 88: 3698-3703
- Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant.Ann. Intern Med. 1998; 129: 89-93
- Geographic distribution of the 20210 G to A prothrombin variant.Thromb. Haemost. 1998; 79: 706-708
- Cryptogenic stroke: time to determine aetiology.J. Thromb. Haemost. 2008; 6: 549-554
- Risk factors profile and clinical outcome of ischemic stroke patients admitted in a Department of Internal Medicine and classified by TOAST classification.Int. Angiol. 2006; 25: 261-267
- Prognosis after cryptogenic cerebral ischemia in patients with coagulopathies.Cerebrovasc. Dis. 2009; 28: 611-617
- Factor V Leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study.J. Stroke Cerebrovasc. Dis. 2013; 22: 419-423
- Factor V Leiden and intracranial hemorrhage.Blood. 2001; 98: 2875
- Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2011; 42: 227-276
- Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombophilia.J. Thromb. Haemost. 2007; 5: 98-101
- Cigarette smoking as a risk factor for stroke. The Framingham Study.JAMA. 1988; 259: 1025-1029
- Meta-analysis of relation between cigarette smoking and stroke.BMJ. 1989; 298: 789-794
- How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-attributable Disease: A Report of the Surgeon General, Atlanta (GA). 2010
- Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults.Stroke. 2005; 36: 533-539
- Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke.J. Neurol. Neurosurg. Psychiatry. 2003; 74: 1615-1620
- A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women.Blood. 1997; 90: 1747-1750
- Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years.Stroke. 2005; 36: 1405-1409
- Lipoprotein (a) as a cardiovascular risk factor: current status.Eur. Heart J. 2010; 31: 2844-2853
- Prothrombin antigen levels in symptomatic and asymptomatic carriers of the 20210A prothrombin variant.Br. J. Haematol. 1998; 103: 1045-1050
Article info
Publication history
Published online: April 10, 2015
Accepted:
April 9,
2015
Received in revised form:
April 8,
2015
Received:
November 20,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
