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Atherosclerosis. 2010 Feb;208(2):437-41. doi: 10.1016/j.atherosclerosis.2009.07.058. Epub 2009 Aug 8.

Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia.

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  • 1Unitat de Lípids, Servei d'Endocrinologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Villarroel 160, 08036 Barcelona, Spain.



Defects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH.


In 436 Spanish FH patients (223 men and 213 women, age 44+/-14 years) with known LDLR mutations, alleles were classified by standard criteria as null (n=269), defective (n=162), or undetermined (n=5). LDLR defects were detected using a microarray (Lipochip) designed to uncover prevalent mutations in Spain and gene sequencing when no mutations were detected. Carotid IMT and plaque were assessed in FH patients and 268 healthy subjects.


All carotid measurements were increased in FH patients versus controls (p<0.05), irrespective of genotype. After adjustment for gender and age, patients with null alleles compared with defective alleles had similar mean and maximum common carotid artery (CCA) IMT, but higher maximum IMT at any carotid segment, with median values (95% confidence interval) of 1.25 mm (1.19-1.31) and 1.11 mm (1.05-1.18), respectively. Multivariate analysis showed that null alleles were independently associated with maximum CCA-IMT (beta=0.09, p=0.033) with an impact similar to that of gender (beta=0.10, p=0.035).


FH patients show advanced carotid atherosclerosis in relation to LDLR mutational class. The findings support the utility of genetic testing in FH beyond providing a secure diagnosis.

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