title: Novel mutations identification in exon 4 of LDLR gene in patients with moderate hypercholesterolemia in a Venezuelan population.
abstract: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by increase in low-density lipoprotein (LDL) cholesterol levels and premature coronary artery disease. In Venezuela, the molecular basis of FH has not been characterized, thus, the aim of this study was to investigate mutations in the exon 4 of the LDLR (LDL-receptor) gene in 225 Venezuelan mixed race individuals (65 hypercholesterolemic and 160 normolipidemic). The exon 4 of the LDLR gene was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Additionally, ApoB-100 gene mutations were investigated. Different LDLR gene mutations were identified in 5 hypercholesterolemic patients (7.7%), 3 missense mutations (4.6%), and 2 frameshift mutations (3%). All mutations were heterozygous. The missense mutations included the amino acid substitution p.E180K, p.R194S, and p.C152G. The frameshift mutations are caused by insertions resulting in the creation of stop codons: p.D157fsX158 and p.S173fsX174, which could code for truncated LDLR of 157 and 173 amino acids, respectively. The apoB gene mutations were not detected in any of our patients and to our knowledge 4 mutations identified in this study have not been reported previously, this study being the first comprehensive mutation analysis of the LDLR causing FH in our region. The early identification of individuals at risk allows changes in lifestyle, including dietary intervention, followed by drug treatment.
authors.affiliation: Endocrine and Metabolic Diseases Research Center, University of Zulia, Maracaibo, Venezuela. narraiz@cantv.net
authors.forename: Nailet
authors.initials: N
authors.lastname: Arráiz
authors.forename: Valmore
authors.initials: V
authors.lastname: Bermúdez
authors.forename: Netxibeth
authors.initials: N
authors.lastname: Rondon
authors.forename: Francia
authors.initials: F
authors.lastname: Reyes
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Borjas
authors.forename: Ernesto
authors.initials: E
authors.lastname: Solís
authors.forename: Endrina
authors.initials: E
authors.lastname: Mujica
authors.forename: Carem
authors.initials: C
authors.lastname: Prieto
authors.forename: Nadia
authors.initials: N
authors.lastname: Reyna
authors.forename: Manuel
authors.initials: M
authors.lastname: Velasco
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D053299:Apolipoprotein B-100 / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014687:Venezuela; D055815:Young Adult
chemical_list: D053299:Apolipoprotein B-100; D011973:Receptors, LDL