title: Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: consecutive survivors and population-based controls.
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.
authors.affiliation: Center for Cardiovascular Prevention, First Medical School of Charles University in Prague and Thomayer Hospital, Czech Republic. Electronic address: alena.krajcoviechova@ftn.cz.
authors.forename: A
authors.initials: A
authors.lastname: Krajcoviechova
authors.affiliation: Center for Cardiovascular Prevention, First Medical School of Charles University in Prague and Thomayer Hospital, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Wohlfahrt
authors.affiliation: 2nd Department of Internal Medicine, Charles University Medical Faculty and Teaching Hospital, Pilsen, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Mayer
authors.affiliation: 2nd Department of Internal Medicine, Charles University Medical Faculty and Teaching Hospital, Pilsen, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Vanek
authors.affiliation: Central Laboratory for Hematology and Thrombotic Centre, First Medical School of Charles University in Prague and General Teaching Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Hajkova
authors.affiliation: Department of Neurology of Thomayer Hospital in Prague, Czech Republic.
authors.forename: D
authors.initials: D
authors.lastname: Hlinovsky
authors.affiliation: Central Laboratory for Hematology and Thrombotic Centre, First Medical School of Charles University in Prague and General Teaching Hospital, Prague, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Kvasnicka
authors.affiliation: Montreal University Hospital Research Center, CRCHUM, Montreal, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Tremblay
authors.affiliation: Montreal University Hospital Research Center, CRCHUM, Montreal, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Hamet
authors.affiliation: 2nd Department of Internal Medicine, Charles University Medical Faculty and Teaching Hospital, Pilsen, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Filipovsky
authors.affiliation: Central Laboratory for Hematology and Thrombotic Centre, First Medical School of Charles University in Prague and General Teaching Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kvasnicka
authors.affiliation: Center for Cardiovascular Prevention, First Medical School of Charles University in Prague and Thomayer Hospital, Czech Republic.
authors.forename: R
authors.initials: R
authors.lastname: Cifkova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019851:Thrombophilia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D011516:Prothrombin
keywords: Factor V Leiden (rs6025); Genetic epidemiology; Hypercoagulopathy; Ischemic stroke; Prothrombin G20210A (rs1799963); Smoking