Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina

• Autores: Bañares, Virginia Gabriela; Corral, Pablo; Medeiros, Ana Margarida; Araujo, María Beatriz; Lozada, Alfredo; Bustamante, Juan Pablo; Cerretini, Roxana; Lopez, Graciela Ines; Bourbon, Mafalda; Schreier, Laura Ester
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: APOB; ARGENTINA; CARDIOVASCULAR DISEASE; CARDIOVASCULAR DISEASE PREVENTION; CHOLESTEROL; FAMILIAL HYPERCHOLESTEROLEMIA; GENETIC VARIANTS; LDLR GENE; MUTATIONS; PUBLIC HEALTH
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Bañares, Virginia Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; Argentina
Fil: Corral, Pablo. Universidad de la Fraternidad de Agrupaciones "santo Tomas de Aquino". Facultad de Ciencias Medicas.; Argentina
Fil: Medeiros, Ana Margarida. Instituto Nacional de Saúde Dr Ricardo Jorge; Portugal
Fil: Araujo, María Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Lozada, Alfredo. Universidad Austral. Hospital Universitario Austral; Argentina
Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Cerretini, Roxana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; Argentina
Fil: Lopez, Graciela Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Bourbon, Mafalda. Instituto Nacional de Saúde Dr Ricardo Jorge; Portugal
Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina