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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1475.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Genetic Determinants of Cardiovascular Disease Risk in Familial Hypercholesterolemia

Angelique C.M. Jansen; Emily S. van Aalst-Cohen; Michael W.T. Tanck; Suzanne Cheng; Marcel R. Fontecha; Jia Li; Joep C. Defesche; John J.P. Kastelein

From the Departments of Vascular Medicine (A.C.M.J., E.S.v.A.-C., J.C.D., J.J.P.K.) and Clinical Epidemiology and Biostatistics (M.W.T.T.), Academic Medical Center, University of Amsterdam, the Netherlands; and the Department of Human Genetics (S.C., M.R.F., J.L.), Roche Molecular Systems, Inc, Alameda, Calif.

Correspondence to John J.P. Kastelein, Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, P.O.Box 22700, room F4-159.2, 1100 DE Amsterdam, the Netherlands. E-mail e.vandongen{at}amc.uva.nl

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).

Methods and 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.

We investigated the contribution of 65 polymorphisms in 36 candidate genes to CVD risk in FH patients and found that the G20210A polymorphism in the prothrombin gene was associated with CVD risk. Our results constitute a step forward in the unraveling of the hereditary propensity toward CVD in FH.

Key Words: cardiovascular disease • genetics • hypercholesterolemia • risk factors

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