Naslov
Genetic analysis of the LDL receptor gene in Croatian hypercholesterolemic patients

Autori
Gornik, Olga ; Zrinski-Topić, Renata ; Sertić, Jadranka ; Flögel, Mirna ; Stavljenić-Rukavina, Ana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2nd Scientific Symposium with International Participation '45 years of molecular biology in Croatia - 50 years of double helix', Book of Abstracts / Ambriović Ristov, Andreja ; Brozović, Anamarija - Zagreb : Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu, 2003, 46-47

Skup
2nd Scientific Symposium with International Participation '45 years of molecular biology in Croatia - 50 years of double helix'

Mjesto i datum
Zagreb, Hrvatska, 20.11.2003. - 21.11.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
LDL receptor gene; hypercholesterolemia; polymorphism; mutations

Sažetak
The LDL-receptor is a cell surface glycoprotein that regulates the plasma cholesterol level by specific uptake of LDL particles. Mutations in LDL-receptor gene cause an elevation of plasma LDL and clinical phenotype of familial hypercholesterolemia (FH). More than 700 of different mutations have been identified worldwide and are heterogeneous in most populations. The aim of the study was to determine the presence and delineate the mutation spectrum of FH patients in Croatia. 249 hypercholesterolemic patients were selected (LDL-cholesterol level above 4.0 mmol/L). Promoter region and all 18 exons of the LDL-receptor gene were screened for changes by SSCP. Detected changes were than additionally characterized by DNA sequencing method. Molecular changes in the LDL-receptor gene were found in 68% of the patients. Six different LDL-receptor gene mutations were observed in 30 of them. Four mutations were found in the ligand-binding domain while the remaining two were located in the epidermal growth factor homology domain that mediates receptor recycling. Mutation in LDL receptor gene that results in Cys127Arg change, named FH-Zagreb, is newly found defect of this gene. In the rest of the patients with molecular changes, genetic polymorphisms 81 T>C, 1413 G>A, 1773 T>C and 1959 C>T were detected. 26% of these patients showed two or more of these polymorphisms simultaneously. Our results offer better insight into the molecular basis of FH in Croatia and shown its heterogeneous nature. They give further understanding of FH pathogenesis and facilitate the selection of the most appropriate diagnostic approach for genetic hypercholesterolemia.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA