Replacement of cysteine at position 46 in the first cysteine-rich repeat of the LDL receptor impairs apolipoprotein recognition.

ABSTRACT:

Background and aims

Pathogenic mutations in the Low Density Lipoprotein Receptor gene (LDLR) cause Familial Hypercholesterolemia (FH), one of the most common genetic disorders with a prevalence as high as 1 in 200 in some populations. FH is an autosomal dominant disorder of lipoprotein metabolism characterized by high blood cholesterol levels, deposits of cholesterol in peripheral tissues such as tendon xanthomas and accelerated atherosclerosis. To date, 2500 LDLR variants have been identified in the LDLR gene; however, only a minority of them have been experimentally characterized and proven to be pathogenic. Here we investigated the role of Cys46 located in the first repeat of the LDL receptor binding domain in recognition of apolipoproteins.

Methods

Activity of the p.(Cys

SUBMITTER: Benito-Vicente A 

PROVIDER: S-EPMC6192581 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature