Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina

• Autores: Bañares, Virginia; Corral, Pablo; Medeiros, Ana Margarida; Araujo, Maria B; Lozada, Alfredo; Bustamante, Juan; Cerretini, Roxana; Lopez, Graciela I; Bourbon, Mafalda; Schreier, L.
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of clinical lipidology 2017;11(2):524-531; pdf
• Materia: Hiperlipoproteinemia Tipo II; Proteína Asociada a Proteínas Relacionadas con Receptor de LDL; Colesterol; Variantes Farmacogenómicas; Mutación; Apolipoproteínas B; Enfermedades Cardiovasculares; Salud Pública
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Bañares, Virginia G. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Departamento de Genética Experimental; Argentina.
Fil: Corral, Pablo. Universidad FASTA. Facultad de Medicina. Departamento Investigación; Argentina.
Fil: Medeiros, Ana Margarida. Instituto Nacional de Saúde Dr Ricardo Jorge. Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis. Grupo de Investigação Cardiovascular. University of Lisbon. BioISI - Biosystems & Integrative Sciences Institute. Faculty of Sciences; Portugal.
Fil: Araujo, Maria Beatriz. Hospital Garrahan. Servicio de Nutrición, Ciudad Autónoma de Buenos Aires; Argentina.
Fil: Lozada, Alfredo. Universidad Austral. Clínica de Lípidos; Argentina.
Fil: Bustamante, Juan. IQUIBICEN-CONICET. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina.
Fil: Cerretini, Roxana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Departamento de Genética Experimental; Argentina.
Fil: Lopez, Graciela I. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica. Laboratorio de Lípidos y Aterosclerosis; Argentina; Universidad de Buenos Aires, Instituto de Fisiopatologia y Bioquímica Clinica - INFIBIOC; Argentina.
Fil: Bourbon, Mafalda. Instituto Nacional de Saúde Dr Ricardo Jorge. Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis. Grupo de Investigação Cardiovascular. University of Lisbon. BioISI - Biosystems & Integrative Sciences Institute. Faculty of Sciences; Portugal.
Fil: Schreier, Laura E. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica. Laboratorio de Lípidos y Aterosclerosis; Argentina; Universidad de Buenos Aires, Instituto de Fisiopatologia y Bioquímica Clinica - INFIBIOC; Argentina.
Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. Objective: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. Methods: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. Results: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics' analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. Conclusion: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype-phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina. Keywords: APOB; Argentina; Cardiovascular disease; Cardiovascular disease prevention; Cholesterol; Familial hypercholesterolemia; Genetic variants; LDLR gene; Mutations; Public health.