Ivette Cruz-Bautista1,2, Alicia Huerta-Chagoya3,4, Hortensia Moreno-Macías3,5, Rosario Rodríguez-Guillén3, María Luisa Ordóñez-Sánchez3, Yayoi Segura-Kato3, Roopa Mehta1,2, Paloma Almeda-Valdés1,2, Lizeth Gómez-Munguía1, Ximena Ruiz-De Chávez2, Ximena Rosas-Flota2, Arali Andrade-Amado2, Bárbara Bernal-Barroeta2, María Guadalupe López-Carrasco2, Luz Elizabeth Guillén-Pineda2, Angelina López-Estrada2, Daniel Elías-López1,2, Alexandro J Martagón-Rosado1,6, Donají Gómez-Velasco1, Cesar Ernesto Lam-Chung2, Omar Yaxmehen Bello-Chavolla1,7, Fabiola Del Razo-Olvera1,2, Lucely D Cetina-Pérez8, José Luis Acosta-Rodríguez9, María Teresa Tusié-Luna3, Carlos A Aguilar-Salinas10,11,12. 1. Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. 2. Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. 3. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán e Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico. 4. CONACyT. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 5. Departamento de Economía, Universidad Autónoma Metropolitana, Mexico City, Mexico. 6. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, 64710, Monterrey, NL, Mexico. 7. Research Division, Instituto Nacional de Geriatría, Mexico City, Mexico. 8. Departamento de Oncología Médica, Instituto Nacional de Cancerología, Mexico City, Mexico. 9. Departamento de Biotecnología Agrícola, Instituto Politécnico Nacional, Mexico City, Mexico. 10. Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. caguilarsalinas@yahoo.com. 11. Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. caguilarsalinas@yahoo.com. 12. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, 64710, Monterrey, NL, Mexico. caguilarsalinas@yahoo.com.
Abstract
BACKGROUND: Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. METHODS: This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. RESULTS: Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901-0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. CONCLUSIONS: The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.
BACKGROUND:Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. METHODS: This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. RESULTS:Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901-0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. CONCLUSIONS: The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.
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Authors: François Mach; Colin Baigent; Alberico L Catapano; Konstantinos C Koskinas; Manuela Casula; Lina Badimon; M John Chapman; Guy G De Backer; Victoria Delgado; Brian A Ference; Ian M Graham; Alison Halliday; Ulf Landmesser; Borislava Mihaylova; Terje R Pedersen; Gabriele Riccardi; Dimitrios J Richter; Marc S Sabatine; Marja-Riitta Taskinen; Lale Tokgozoglu; Olov Wiklund Journal: Eur Heart J Date: 2020-01-01 Impact factor: 29.983
Authors: Arthur Ko; Rita M Cantor; Daphna Weissglas-Volkov; Elina Nikkola; Prasad M V Linga Reddy; Janet S Sinsheimer; Bogdan Pasaniuc; Robert Brown; Marcus Alvarez; Alejandra Rodriguez; Rosario Rodriguez-Guillen; Ivette C Bautista; Olimpia Arellano-Campos; Linda L Muñoz-Hernández; Veikko Salomaa; Jaakko Kaprio; Antti Jula; Matti Jauhiainen; Markku Heliövaara; Olli Raitakari; Terho Lehtimäki; Johan G Eriksson; Markus Perola; Kirk E Lohmueller; Niina Matikainen; Marja-Riitta Taskinen; Maribel Rodriguez-Torres; Laura Riba; Teresa Tusie-Luna; Carlos A Aguilar-Salinas; Päivi Pajukanta Journal: Nat Commun Date: 2014-06-02 Impact factor: 14.919