Artículo

Bañares, V.G.; Corral, P.; Medeiros, A.M.; Araujo, M.B.; Lozada, A.; Bustamante, J.; Cerretini, R.; López, G.; Bourbon, M.; Schreier, L.E."Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina" (2017) Journal of Clinical Lipidology. 11(2):524-531
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Abstract:

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. © 2017 National Lipid Association

Registro:

Documento: Artículo
Título:Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina
Autor:Bañares, V.G.; Corral, P.; Medeiros, A.M.; Araujo, M.B.; Lozada, A.; Bustamante, J.; Cerretini, R.; López, G.; Bourbon, M.; Schreier, L.E.
Filiación:Departamento de Genética Experimental, Centro Nacional de Genética Médica, Administración Nacional de Laboratorios e Institutos de Salud –ANLIS, “Dr Carlos Malbrán”, Ciudad Autónoma de Buenos Aires, Argentina
Departamento Investigación, Facultad de Medicina, Universidad FASTA, Buenos Aires, Argentina
Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, Portugal
Faculty of Sciences, University of Lisbon, BioISI – Biosystems & Integrative Sciences Institute, Lisboa, Portugal
Servicio de Nutrición, Hospital Nacional de Pediatría “Dr Juan P. Garraham”, Ciudad Autónoma de Buenos Aires, Argentina
Clínica de Lípidos, Universidad Austral, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
Facultad de Ingeniería, Universidad Nacional de Entre RíosEntre Ríos, Argentina
Laboratorio de Lípidos y Aterosclerosis, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Buenos Aires, Argentina
Universidad de Buenos Aires, Instituto de Fisiopatologia y Bioquímica Clinica, INFIBIOC, Buenos Aires, Argentina
Palabras clave:APOB; Argentina; Cardiovascular disease; Cardiovascular disease prevention; Cholesterol; Familial hypercholesterolemia; Genetic variants; LDLR gene; Mutations; Public health; asparagine; calcium ion; low density lipoprotein receptor; low density lipoprotein receptor; adolescent; adult; aged; Argentina; Article; bioinformatics; child; clinical article; exon; familial hypercholesterolemia; female; gene mutation; gene sequence; genetic analysis; genetic identification; genetic variability; heterozygote; homozygote; human; male; multiplex ligation dependent probe amplification; priority journal; sequence alignment; chemistry; familial hypercholesterolemia; genetic variation; genetics; metabolism; middle aged; molecular model; preschool child; protein conformation; young adult; Adolescent; Adult; Aged; Argentina; Child; Child, Preschool; Female; Genetic Variation; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Models, Molecular; Protein Conformation; Receptors, LDL; Young Adult
Año:2017
Volumen:11
Número:2
Página de inicio:524
Página de fin:531
DOI: http://dx.doi.org/10.1016/j.jacl.2017.02.007
Handle:http://hdl.handle.net/20.500.12110/paper_19332874_v11_n2_p524_Banares
Título revista:Journal of Clinical Lipidology
Título revista abreviado:J. Clin. Lipidology
ISSN:19332874
CAS:asparagine, 70-47-3, 7006-34-0; calcium ion, 14127-61-8; Receptors, LDL
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19332874_v11_n2_p524_Banares

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Citas:

---------- APA ----------
Bañares, V.G., Corral, P., Medeiros, A.M., Araujo, M.B., Lozada, A., Bustamante, J., Cerretini, R.,..., Schreier, L.E. (2017) . Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina. Journal of Clinical Lipidology, 11(2), 524-531.
http://dx.doi.org/10.1016/j.jacl.2017.02.007
---------- CHICAGO ----------
Bañares, V.G., Corral, P., Medeiros, A.M., Araujo, M.B., Lozada, A., Bustamante, J., et al. "Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina" . Journal of Clinical Lipidology 11, no. 2 (2017) : 524-531.
http://dx.doi.org/10.1016/j.jacl.2017.02.007
---------- MLA ----------
Bañares, V.G., Corral, P., Medeiros, A.M., Araujo, M.B., Lozada, A., Bustamante, J., et al. "Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina" . Journal of Clinical Lipidology, vol. 11, no. 2, 2017, pp. 524-531.
http://dx.doi.org/10.1016/j.jacl.2017.02.007
---------- VANCOUVER ----------
Bañares, V.G., Corral, P., Medeiros, A.M., Araujo, M.B., Lozada, A., Bustamante, J., et al. Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina. J. Clin. Lipidology. 2017;11(2):524-531.
http://dx.doi.org/10.1016/j.jacl.2017.02.007