title: The role of classic risk factors and prothrombotic factor gene mutations in ischemic stroke risk development in young and middle-aged individuals.
abstract: BACKGROUND
  In young individuals, a genetically predisposing hypercoagulability and classic modifying risk factors can act synergistically on the ischemic stroke risk development. The aim of the study was to compare the prevalence of classic vascular risk factors and polymorphisms of the G20210A coagulation factor II (prothrombin), Arg506Glu coagulation factor V Leiden, C677T methylenetetrahydrofolate reductase (MTHFR), and 4G/5G plasminogen activator inhibitor-1 (PAI-1) and the impact of these gene mutations and classic vascular risk factors on the overall stroke risk in individuals aged 55 years or younger.
  
  
  METHODS
  The study included 155 stroke patients aged 55 years or younger and 150 control subjects. Stroke prevalence and odds ratio (OR) were assessed for the following parameters: G20210A prothrombin, Arg506Glu factor V Leiden, C677T MTHFR, and 4G/5G PAI-1 polymorphisms; total number of study polymorphisms in a particular subject (genetic sum); and classic vascular risk factors of hypertension, obesity, diabetes mellitus, cigarette smoking, hypercholesterolemia, hypertriglyceridemia, and elevated levels of low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein cholesterol.
  
  
  RESULTS
  The prevalence of hypertension (P < .001), smoking (P < .001), decreased HDL cholesterol levels (P < .001), obesity (P = .001), elevated LDL cholesterol (P = .036), C677T MTHFR polymorphism (P < .001), and genetic sum was significantly higher in the group of stroke patients. The following parameters were found to act as independent risk factors for ischemic stroke: decreased HDL cholesterol level (P < .001; OR 4.618; 95% confidence interval [CI] 2.381-8.957); hypertension (P = .001; OR 2.839; 95% CI 1.519-5.305); obesity (P = .040; OR 2.148; 95% CI 1.036-4.457); smoking (P = .001; OR 2.502; 95% CI 1.436-4.359); and genetic sum as a continuous variable (P < .01; OR 2.307; 95% CI 1.638-3.250).
  
  
  CONCLUSIONS
  Gene mutations of the procoagulable and proatherosclerotic factors investigated exerted a synergistic action in the development of overall risk of ischemic stroke in young and middle-aged individuals.
authors.affiliation: University Department of Neurology, Sestre milosrdnice University Hospital Center, Zagreb. Electronic address: visnjasupanc@inet.hr.
authors.forename: Visnja
authors.initials: V
authors.lastname: Supanc
authors.affiliation: Department of Medical Statistics, Epidemiology, and Medical Informatics, Andrija Stampar School of Public Health, University of Zagreb School of Medicine, Zagreb.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Sonicki
authors.affiliation: University Department of Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
authors.forename: Ines
authors.initials: I
authors.lastname: Vukasovic
authors.affiliation: University Department of Neurology, Sestre milosrdnice University Hospital Center, Zagreb.
authors.forename: Vesna V
authors.initials: VV
authors.lastname: Solter
authors.affiliation: University Department of Neurology, Sestre milosrdnice University Hospital Center, Zagreb.
authors.forename: Iris
authors.initials: I
authors.lastname: Zavoreo
authors.affiliation: University Department of Neurology, Sestre milosrdnice University Hospital Center, Zagreb.
authors.forename: Vanja B
authors.initials: VB
authors.lastname: Kes
mesh_terms: D000328:Adult; D000367:Age Factors; D001777:Blood Coagulation / Q000235:genetics*; D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017523:Croatia / Q000453:epidemiology; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D015995:Prevalence; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D019851:Thrombophilia / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Genetics; ischemic stroke; risk factors; young adults