TY - JOUR
T1 - Novel mutations identification in exon 4 of LDLR gene in patients with moderate hypercholesterolemia in a venezuelan population
AU - Arráiz, Nailet
AU - Bermúdez, Valmore
AU - Rondon, Netxibeth
AU - Reyes, Francia
AU - Borjas, Lisbeth
AU - Solís, Ernesto
AU - Mujica, Endrina
AU - Prieto, Carem
AU - Reyna, Nadia
AU - Velasco, Manuel
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Coronary artery disease
KW - Familial hypercholesterolemia
KW - Frameshift mutations
KW - LDL-receptor
KW - PCR-SSCP
UR - http://www.scopus.com/inward/record.url?scp=77952482114&partnerID=8YFLogxK
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U2 - 10.1097/MJT.0b013e3181c1234d
DO - 10.1097/MJT.0b013e3181c1234d
M3 - Article
C2 - 20019594
AN - SCOPUS:77952482114
SN - 1075-2765
VL - 17
SP - 325
EP - 329
JO - American journal of therapeutics
JF - American journal of therapeutics
IS - 3
ER -