title: Association between variations in coagulation system genes and carotid plaque.
abstract: OBJECTIVE
  Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes.
  
  
  METHODS
  From the Genetic Determinants of Subclinical Carotid Disease Study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r(2)>0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p ≤ 0.01) was performed in an independent sample of 301 Dominicans.
  
  
  RESULTS
  The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65 ± 8 discovery; 65 ± 9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p ≤ 0.01) with plaque size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p ≤ 0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses.
  
  
  CONCLUSIONS
  Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.forename: Ashley
authors.initials: A
authors.lastname: Beecham
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Dong
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
authors.forename: Mark S
authors.initials: MS
authors.lastname: McClendon
authors.forename: Hannah
authors.initials: H
authors.lastname: Gardener
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
mesh_terms: D017668:Age of Onset; D000368:Aged; D001777:Blood Coagulation / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D004293:Dominican Republic / Q000208:ethnology; D050171:Dyslipidemias / Q000453:epidemiology; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D019700:Thrombospondin 1 / Q000235:genetics* / Q000502:physiology; D014463:Ultrasonography; D014841:von Willebrand Factor / Q000235:genetics* / Q000502:physiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D019700:Thrombospondin 1; D014841:von Willebrand Factor