MUTATIONS IN THE HUMAN PCSK9 GENE ASSOCIATED TO HYPERCHOLESTEROLEMIA

摘要

An isolated or recombinant PCSK9 gene or its fragment and/or an isolated or purified Neural Apoptosis Regulated Convertase 1 (NARC-1) protein or its fragment comprising alterations, is new. An isolated or recombinant PCSK9 gene or its fragment comprising an alteration, where the alteration is a substitution at nucleotide 625 and/or 890 of a sequence comprising 3617 bp (SEQ ID NO: 1) fully defined in the specification, or selected from polymorphisms given in the specification, and/or an isolated or purified NARC-1 protein or its fragment comprising an alteration, where the alteration is an insertion of a residue Leucine at position 15 of a sequence comprising 692 amino acids (SEQ ID NO: 2) fully defined in the specification, a substitution of the residue Arginine at position 46 of SEQ ID NO: 2 by a Leucine, a substitution of the residue Alanine at position 53 of SEQ ID NO: 2 by a Valine, a substitution of the residue Serine at position 127 of SEQ ID NO: 2 by an Arginine, a substitution of the residue Phenylalanine at position 216 of SEQ ID NO: 2 by a Leucine, a substitution of the residue isoleucine at position 474 of SEQ ID NO: 2 by a Valine, a substitution of the residue Glutamic acid at position 670 of SEQ ID NO: 2 by a Glycine or their combination. Independent claims are also included for: (1) a method of genotyping at least one polymorphism; (2) a method of detecting the presence of or predisposition to hypercholesterolemia, more particularly autosomal dominant hypercholesterolemia (ADH), lipid and lipoprotein metabolism disorders, atherosclerosis, or cardiovascular disease (CVD) in a subject; (3) a method of selecting biologically active compounds; and (4) a diagnostic kit comprising primers, probes and/or antibodies for detecting in a sample from a subject the presence of an alteration in the PCSK9 gene or in the NARC-1 protein. ACTIVITY : Antilipemic; Antiarteriosclerotic; Cardiovascular-Gen. No biological data given. MECHANISM OF ACTION : NARC-Modulator-1; Gene therapy.