Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia.
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.
Jansen
Angelique C M
AC
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
van Aalst-Cohen
Emily S
ES
Tanck
Michael W T
MW
Cheng
Suzanne
S
Fontecha
Marcel R
MR
Li
Jia
J
Defesche
Joep C
JC
Kastelein
John J P
JJ
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