title: Type of LDLR mutation and the pharmacogenetics of familial hypercholesterolemia treatment.
abstract: Familial hypercholesterolemia (FH) is an autosomal dominant disease mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. FH patients present a wide variability regarding response to drugs and they are usually undertreated. Here, we review studies that evaluated the association between the type of LDLR mutation and the response to lipid-lowering therapy. The main findings were that patients with a null LDLR mutation had: higher baseline LDL-C, higher LDL-C after drug therapy, lower proportion of patients within the LDL-C target value and higher frequencies of CVD. Thus, we conclude that FH patients harboring a null mutation have a trend to an increased risk, even if diagnosis is early established and lipid-lowering treatment instituted. It is suggested that these individuals may benefit from the use of newly approved lipid-lowering agents.
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Brazil., Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César - São Paulo - SP., CEP 05403-000, Brazil.
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Brazil., Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César - São Paulo - SP., CEP 05403-000, Brazil.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D000924:Anticholesteremic Agents; C573412:LDLR protein, human; D011973:Receptors, LDL
keywords: LDLR mutation; familial hypercholesterolemia; lipid-lowering therapy; pharmacogenomics; type of mutation