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  • Title: Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia.
    Author: Jansen AC, van Aalst-Cohen ES, Tanck MW, Cheng S, Fontecha MR, Li J, Defesche JC, Kastelein JJ.
    Journal: Arterioscler Thromb Vasc Biol; 2005 Jul; 25(7):1475-81. PubMed ID: 15879303.
    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). 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.
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