Isabel De Castro-Orós1, Ana Cenarro2, María Teresa Tejedor2, Lucía Baila-Rueda2, Rocío Mateo-Gallego2, Itziar Lamiquiz-Moneo2, Miguel Pocoví2, Fernando Civeira2. 1. From the Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis y Laboratorio de Investigación Molecular. Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain (I.D.C.-O., A.C., L.B.-R., R.M.-G., I.L.-M., F.C.); Departamento de Anatomía, Embriología y Genética (M.T.T.) and Departamento de Bioquímica y Biología Molecular y Celular (M.P.), Universidad de Zaragoza, Zaragoza, Spain. idecastro.iacs@aragon.es. 2. From the Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis y Laboratorio de Investigación Molecular. Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain (I.D.C.-O., A.C., L.B.-R., R.M.-G., I.L.-M., F.C.); Departamento de Anatomía, Embriología y Genética (M.T.T.) and Departamento de Bioquímica y Biología Molecular y Celular (M.P.), Universidad de Zaragoza, Zaragoza, Spain.
Abstract
BACKGROUND: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined. METHODS AND RESULTS: This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of APOE, APOA5, GALNTN2, and GCKR variants were positively correlated with plasma triglycerides, whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL. CONCLUSIONS: Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.
BACKGROUND: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined. METHODS AND RESULTS: This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of APOE, APOA5, GALNTN2, and GCKR variants were positively correlated with plasma triglycerides, whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL. CONCLUSIONS: Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.
Authors: Itziar Lamiquiz-Moneo; Cristian Blanco-Torrecilla; Ana M Bea; Rocío Mateo-Gallego; Sofía Pérez-Calahorra; Lucía Baila-Rueda; Ana Cenarro; Fernando Civeira; Isabel de Castro-Orós Journal: Lipids Health Dis Date: 2016-04-23 Impact factor: 3.876
Authors: Ben van Ommen; Tim van den Broek; Iris de Hoogh; Marjan van Erk; Eugene van Someren; Tanja Rouhani-Rankouhi; Joshua C Anthony; Koen Hogenelst; Wilrike Pasman; André Boorsma; Suzan Wopereis Journal: Nutr Rev Date: 2017-08-01 Impact factor: 7.110
Authors: A M Bea; E Franco-Marín; V Marco-Benedí; E Jarauta; I Gracia-Rubio; A Cenarro; F Civeira; I Lamiquiz-Moneo Journal: Sci Rep Date: 2021-03-26 Impact factor: 4.379
Authors: Danish Saleheen; Angela M Wood; Julian L Griffin; Albert Koulman; Eric L Harshfield; Eric B Fauman; David Stacey; Dirk S Paul; Daniel Ziemek; Rachel M Y Ong; John Danesh; Adam S Butterworth; Asif Rasheed; Taniya Sattar; Imran Saleem; Zoubia Hina; Unzila Ishtiaq; Nadeem Qamar; Nadeem Hayat Mallick; Zia Yaqub; Tahir Saghir; Syed Nadeem Hasan Rizvi; Anis Memon; Mohammad Ishaq; Syed Zahed Rasheed; Fazal-Ur-Rehman Memon; Anjum Jalal; Shahid Abbas; Philippe Frossard Journal: BMC Med Date: 2021-09-10 Impact factor: 8.775