AIM: This study aims to assess whether epigenetic changes may account for high-density lipoprotein cholesterol (HDL-C) level variability in familial hypercholesterolemia (FH), a recognized human model to study cardiovascular disease risk modulators. MATERIALS & METHODS: A genome-wide DNA methylation analysis (Infinium HumanMethylation27 BeadChip, Illumina) was performed on peripheral blood DNA samples obtained from men with FH with low (n = 10) or high (n = 11) HDL-C concentrations. The initial association with one of the top differentially methylated loci located in the promoter of the TNNT1 gene was replicated in a cohort of 276 FH subjects using pyrosequencing. RESULTS: According to the Ingenuity Pathway Analysis software, the HDL-C differentially methylated loci identified were significantly associated with pathways related to lipid metabolism and cardiovascular disease. TNNT1 DNA methylation levels were positively correlated with mean HDL particle size, HDL-phospholipid, HDL-apolipoprotein AI, HDL-C and TNNT1 expression levels. CONCLUSION: These results suggest that epigenome-wide changes account for interindividual variations in HDL particle metabolism and that TNNT1 is a new candidate gene for dyslipidemia.
AIM: This study aims to assess whether epigenetic changes may account for high-density lipoprotein cholesterol (HDL-C) level variability in familial hypercholesterolemia (FH), a recognized human model to study cardiovascular disease risk modulators. MATERIALS & METHODS: A genome-wide DNA methylation analysis (Infinium HumanMethylation27 BeadChip, Illumina) was performed on peripheral blood DNA samples obtained from men with FH with low (n = 10) or high (n = 11) HDL-C concentrations. The initial association with one of the top differentially methylated loci located in the promoter of the TNNT1 gene was replicated in a cohort of 276 FH subjects using pyrosequencing. RESULTS: According to the Ingenuity Pathway Analysis software, the HDL-C differentially methylated loci identified were significantly associated with pathways related to lipid metabolism and cardiovascular disease. TNNT1 DNA methylation levels were positively correlated with mean HDL particle size, HDL-phospholipid, HDL-apolipoprotein AI, HDL-C and TNNT1 expression levels. CONCLUSION: These results suggest that epigenome-wide changes account for interindividual variations in HDL particle metabolism and that TNNT1 is a new candidate gene for dyslipidemia.
Authors: Marguerite R Irvin; Degui Zhi; Roby Joehanes; Michael Mendelson; Stella Aslibekyan; Steven A Claas; Krista S Thibeault; Nikita Patel; Kenneth Day; Lindsay Waite Jones; Liming Liang; Brian H Chen; Chen Yao; Hemant K Tiwari; Jose M Ordovas; Daniel Levy; Devin Absher; Donna K Arnett Journal: Circulation Date: 2014-06-11 Impact factor: 29.690
Authors: S Sayols-Baixeras; I Subirana; C Lluis-Ganella; F Civeira; J Roquer; A N Do; D Absher; A Cenarro; D Muñoz; C Soriano-Tárraga; J Jiménez-Conde; J M Ordovas; M Senti; S Aslibekyan; J Marrugat; D K Arnett; R Elosua Journal: Hum Mol Genet Date: 2016-10-15 Impact factor: 6.150
Authors: Eva-Maria Navarrete-Muñoz; Jesus Vioque; Estefanía Toledo; Alejando Oncina-Canovas; Miguel Ángel Martínez-González; Jordi Salas-Salvadó; Dolores Corella; Montserrat Fitó; Dora Romaguera; Ángel M Alonso-Gómez; Julia Wärnberg; J Alfredo Martínez; Luís Serra-Majem; Ramon Estruch; Francisco J Tinahones; José Lapetra; Xavier Pintó; Josep A Tur; José López-Miranda; Aurora Bueno-Cavanillas; Pilar Matía-Martín; Lidia Daimiel; Vicente Martín Sánchez; Josep Vidal; Ana Isabel de Cos Blanco; Emili Ros; Javier Diez-Espino; Nancy Babio; Rebeca Fernandez-Carrion; Olga Castañer; Antoni Colom; Laura Compañ-Gabucio; Itziar Salaverria Lete; Edelys Crespo-Oliva; Itziar Abete; Laura Tomaino; Rosa Casas; José Carlos Fernandez-Garcia; José Manuel Santos-Lozano; Iziar Sarasa; José M Gámez; José M Antonio Garcia-Rios; Sandra Martín-Pelaez; Miguel Ruiz-Canela; Andrés Díaz-López; Raul Martinez-Lacruz; Maria Dolors Zomeño; Elena Rayó; Cristina Gisbert Sellés; Silvia Canudas; Albert Goday; Manoli García-de-la-Hera Journal: Eur J Nutr Date: 2020-08-24 Impact factor: 5.614
Authors: Liliane Pfeiffer; Simone Wahl; Luke C Pilling; Eva Reischl; Johanna K Sandling; Sonja Kunze; Lesca M Holdt; Anja Kretschmer; Katharina Schramm; Jerzy Adamski; Norman Klopp; Thomas Illig; Åsa K Hedman; Michael Roden; Dena G Hernandez; Andrew B Singleton; Wolfgang E Thasler; Harald Grallert; Christian Gieger; Christian Herder; Daniel Teupser; Christa Meisinger; Timothy D Spector; Florian Kronenberg; Holger Prokisch; David Melzer; Annette Peters; Panos Deloukas; Luigi Ferrucci; Melanie Waldenberger Journal: Circ Cardiovasc Genet Date: 2015-01-12