Preliminary spectrum of genetic variants in familial hypercholesterolemia in 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 heal...
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todo:paper_19332874_v11_n2_p524_Banares2023-10-03T16:36:11Z Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina Bañares, V.G. Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. 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 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 JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19332874_v11_n2_p524_Banares |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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 |
| format |
JOUR |
| author |
Bañares, V.G. Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. |
| author_facet |
Bañares, V.G. Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. |
| author_sort |
Bañares, V.G. |
| title |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
| title_short |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
| title_full |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
| title_fullStr |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
| title_full_unstemmed |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
| title_sort |
preliminary spectrum of genetic variants in familial hypercholesterolemia in argentina |
| url |
http://hdl.handle.net/20.500.12110/paper_19332874_v11_n2_p524_Banares |
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1807316095854444544 |