Browsing by Author "Corral, P."
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- Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countriesPublication . Santos, R.D.; Bourbon, M.; Alonso, R.; Cuevas, A.; Vasques-Cardenas, N.A.; Pereira, A.C.; Merchan, A.; Alves, A.C.; Medeiros, A.M.; Jannes, C.E.; Krieger, J.E.; Schreier, L.; Perez de Isla, L.; Magaña-Torres, M.T.; Stoll, M.; Mata, N.; Dell Oca, N.; Corral, P.; Asenjo, S.; Bañares, V.G.; Reyes, X.; Mata, P.; Ibero-American Familial Hypercholesterolemia NetworkBACKGROUND: There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. OBJECTIVE: To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. METHODS: Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America. RESULTS: From a conservative estimation of an FH prevalence of 1 of 500 individuals, there should be 1.2 million heterozygous FH individuals in Ibero-America and roughly 27,400 were diagnosed so far. Only Spain, Brazil, Portugal, and Uruguay have active cascade screening programs. The prevalence of cardiovascular disease ranged from 10% to 42% in member countries, and the highest molecular identification rates are seen in Spain, 8.3%, followed by Portugal, 3.8%, and Uruguay with 2.5%. In the 3 countries with more FH patients identified (Spain, Portugal, and Brazil) between 10 and 15 mutations are responsible for 30% to 47% of all FH cases. Spain and Portugal share 5 of the 10 most common mutations (4 in low density lipoprotein receptor [LDLR] and the APOB3527). Spain and Spanishspeaking Latin American countries share 6 of the most common LDLR mutations and the APOB3527. LDL apheresis is available only in Spain and Portugal and not all countries have specific FH diagnostic and treatment guidelines as well as patient organizations. CONCLUSIONS: Ibero-American countries share similar mutations and gaps in FH care.
- Composición genética de la Hipercolesterolemia Familiar en Argentina en relación a los países de la Red Iberoamericana de HFPublication . Bañares, V.G.; Alves, A.C.; Alonso, R.; Jannes, C.E.; Medeiros, A.M.; Corral, P.; DellOca, N.; Araujo, M.B.; Pereira, A.; Elikir, G.D.; Reyes, X.; Cuevas, A.; Vázquez Cárdenas, A.; Stoll, M.; Santos, R.; Mata, P.; Schreier, L.; Bourbon, MafaldaIntroducción: La Hipercolesterolemia Familiar (HF), de herencia codominante, lleva a la EC temprana debido a los niveles elevados de lipoproteínas de baja densidad (LDL) plasmáticas presentes desde el nacimiento. Funcionalmente el aclaramiento hepático de las LDL se ve disminuído. Se origina por mutaciones en los genes LDLR (94%), APOB (4%), PCSK9 (1%) generalmente y hay más de 1000 variantes patogénicas solo en el LDLR. Los países de iberoamerica (IBA) comparten orígenes y el estudio conjunto de las bases moleculares contribuirá al esclarecimiento de la relación fenotipo / genotipo y mejorará la prognosis de los pacientes, uno de los objetivos de la Red. En IBA se estiman 3 millones de HF que, detectados en forma temprana, podría prevenirse en ellos la EC.
- Familial hypercholesterolaemia: a global call to armsPublication . Vallejo-Vaz, A.J.; Kondapally Seshasai, S.R.; Cole, D.; Hovingh, G.K.; Kastelein, J.J.; Mata, P.; Raal, F.J.; Santos, R.D.; Soran, H.; Watts, G.F.; Abifadel, M.; Aguilar-Salinas, C.A.; Akram, A.; Alnouri, F.; Alonso, R.; Al-Rasadi, K.; Banach, M.; Bogsrud, M.P.; Bourbon, M.; Bruckert, E.; Car, J.; Corral, P.; Descamps, O.; Dieplinger, H.; Durst, R.; Freiberger, T.; Gaspar, I.M.; Genest, J.; Harada-Shiba, M.; Jiang, L.; Kayikcioglu, M.; Lam, C.S.; Latkovskis, G.; Laufs, U.; Liberopoulos, E.; Nilsson, L.; Nordestgaard, B.G.; O'Donoghue, J.M.; Sahebkar, A.; Schunkert, H.; Shehab, A.; Stoll, M.; Su, TC; Susekov, A.; Widén, E.; Catapano, A.L.; Ray, K.K.Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDLreceptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDLcholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1e3]. If left untreated, the relative risk of premature coronary artery disease is significantly higher in heterozygous patients than unaffected individuals, with most untreated homozygotes developing ASCVD before the age of 20 and generally not surviving past 30 years [2e5]. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated, thereby representing a major global public health challenge.
- Genetic Analysis of Familial Hypercholesterolemia in Iberoamerican CountriesPublication . Chora, J.R.; Mata, P.; Santos, R.; Vázquez-Cárdenas, A.; Stoll, M.; Schreier, L.; Cuevas, A.; Alves, A.C.; Medeiros, A.M.; Perez Isla, L.; Jannes, C.; Pereira, A.; Dell'Oca, N.; Reyes, X.; Corral, P.; Bañares, V.; Magaña-Torres, T.; Aguilar-Salinas, C.; Alonso, R.; Bourbon, MafaldaThe Iberoamerican Familial Hypercholesterolemia network (IBAFH_N) was created in 2013 to promote awareness for Familial Hypercholesterolemia (FH) in these countries – Argentina, Brazil, Chile, Mexico, Portugal, Spain, Uruguay and more recently Colombia – that share a past and history. The aim of this work was to perform a molecular analysis of FH mutations in Iberoamerica.
- Molecular aspects of Homozygous Familial Hypercholesterolemia in Iberoamerican CountriesPublication . Alves, A.C.; Alonso, R.; Cuevas, A.; Medeiros, A.M.; Pereira, A.C.; Jannes, C.E.; Krieger, J.E.; Arroyo, R.; Schreier, L.; Corral, P.; Bañares, V.; Araujo, G.M.; Asenjo, S.; Stoll, M.; Dell'Oca, N.; Reyes, X.; Ressia, A.; Campo, R.; Merchan, A.; Magaña-Torres Teresa, M.; Vasques-Cardenas, A.; Mata, N.P.; Santos, R.D.; Bourbon, M.Homozygous Familial Hypercholesterolemia (HoFH) is a rare disorder, affecting 1 in 300,000 to 1,000,000 people in the general population. The Iberoamerican FH (IBAFH) network was constituted in 2013 with the main objectives to promote awareness and education on FH, and to improve and promote early diagnosis and treatment of the disorder in the network countries. In 2018, there are 8 countries (Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain and Uruguay) belonging to the network representing 75% of region’s population. It is estimated that there are 600 to 1,800 HoFH in the Ibero-America, most of them not diagnosed and/or not treated adequately. The Iberoamerican community has an estimated population of 640 million inhabitants. The objective of this work is to describe molecular characteristics of HoFH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay.
- Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies CollaborationPublication . EAS Familial Hypercholesterolaemia Studies Collaboration; Vallejo-Vaz, A.J.; Akram, A.; Kondapally Seshasai, S.R.; Cole, D.; Watts, G.F.; Hovingh, G.K.; Kastelein, J.J.; Mata, P.; Raal, F.J.; Santos, R.D.; Soran, H.; Freiberger, T.; Abifadel, M.; Aguilar-Salinas, C.A.; Alnouri, F.; Alonso, R.; Al-Rasadi, K.; Banach, M.; Bogsrud, M.P.; Bourbon, M.; Bruckert, E.; Car, J.; Ceska, R.; Corral, P.; Descamps, O.; Dieplinger, H.; Do, C.T.; Durst, R.; Ezhov, M.V.; Fras, Z.; Gaita, D.; Gaspar, I.M.; Genest, J.; Harada-Shiba, M.; Jiang, L.; Kayikcioglu, M.; Lam, C.S.; Latkovskis, G.; Laufs, U.; Liberopoulos, E.; Lin, J.; Lin, N.; Maher, V.; Majano, N.; Marais, A.D.; März, W.; Mirrakhimov, E.; Miserez, A.R.; Mitchenko, O.; Nawawi, H.; Nilsson, L.; Nordestgaard, B.G.; Paragh, G.; Petrulioniene, Z.; Pojskic, B.; Reiner, Ž.; Sahebkar, A.; Santos, L.E.; Schunkert, H.; Shehab, A.; Slimane, M.N.; Stoll, M.; Su, T.C.; Susekov, A.; Tilney, M.; Tomlinson, B.; Tselepis, A.D.; Vohnout, B.; Widén, E.; Yamashita, S.; Catapano, A.L.; Ray, K.K.BACKGROUND: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. METHODS: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. CONCLUSIONS: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients.
- Preliminary spectrum of genetic variants in familial hypercholesterolemia in ArgentinaPublication . Bañares, V.G.; Corral, P.; Medeiros, A.M.; Araujo, M.B.; Lozada, A.; Bustamante, J.; Cerretini, R.; López, G.; Bourbon, M.; Schreier, L.E.Highlights: - First description of familial hypercholesterolemia mutations in Argentina; - Identification of 7 patients with severe familial hypercholesterolemia; - Wide genetic heterogeneity with 1 relatively common allele, the Lebanese mutation; Description and deep bioinformatics characterization of 4 novel genetic variants; - Studying the exon 14 in a first step could be a low-cost approach for this population. 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.