Research Article| Volume 240, ISSUE 2, P446-452, June 2015

Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: Consecutive survivors and population-based controls


      • 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.



      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.


      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.


      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.


      In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.



      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)
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