engleski

Low density lipoprotein receptor gene mutations in Croatian hypercholesterolemic patients

Mutations in the LDL-receptor gene cause a marked elevation of plasma cholesterol, in particular of the LDL subfraction, and the clinical phenotype of familial hypercholesterolemia. Mutation analysis was performed in 127 hypercholesterolemic patients from Zagreb. The promoter region and all 18 exons of the LDL-receptor gene were screened using single-strand conformation polymorphism method. The molecular defects detected were then characterized by direct sequencing. Nucleotide changes were detected in 9.4% patients with hypercholesterolemia. About five different mutations in the low-density lipoprotein receptor gene were identified in 12 patients. Four missense mutations (C6W, C127R, D200G and S265T) were located in ligand binding domain and one (G457R) was located in the epidermal growth factor precursor homology domain. One of these mutations, C127R (FH Zagreb), has not been described before in any other population. Five genetic polymorphisms (C6C, A370T, R450R, N570N and V632V) were detected in other. Knowledge of genetic basis of hypercholesterolemia may contribute to designing a specific diagnostic analysis scheme. Therefore, for molecular diagnosis of familial hypercholesterolemia in Croatia, the whole low density lipoprotein receptor gene of each patient must be screened for new and recurrent mutations.

hypercholesterolemia ; low density lipoprotein receptor ; mutations ; single-strand conformation polymorphism

nije evidentirano