title: Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia.
abstract: OBJECTIVE
  To investigate the contribution of polymorphisms in multiple candidate genes to cardiovascular disease (CVD) risk in a large cohort of patients with heterozygous familial hypercholesterolemia (FH).
  
  
  RESULTS
  We genotyped 1940 FH patients for 65 polymorphisms in 36 candidate genes. During 91.451 person-years, 643 (33.1%) patients had at least 1 cardiovascular event. Multifactorial Cox survival analysis revealed that the G20210A polymorphism in the prothrombin gene was strongly associated with a significantly increased CVD risk (GA versus GG; P<0.001).
  
  
  CONCLUSIONS
  In a large cohort of FH patients, we found that the G20210A polymorphism in the prothrombin gene is strongly associated with CVD risk. Our results constitute a step forward in the unraveling of the hereditary propensity toward CVD in FH and might lead to better risk stratification and hence to more tailored therapy for CVD prevention.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Angelique C M
authors.initials: AC
authors.lastname: Jansen
authors.forename: Emily S
authors.initials: ES
authors.lastname: van Aalst-Cohen
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Marcel R
authors.initials: MR
authors.lastname: Fontecha
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors