Montse Guardiola1, Josep Ribalta2. 1. Unitat de Recerca en Lípids i Arteriosclerosi, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. 2. Unitat de Recerca en Lípids i Arteriosclerosi, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. josep.ribalta@urv.cat.
Abstract
PURPOSE OF REVIEW: This review is intended to summarize the genetic studies published during the last 3 years that help us understand the physiology of apoAV and its clinical implications. RECENT FINDINGS: APOA5 is probably the gene with the strongest effect on triglyceride (TG) metabolism. APOA5 is almost exclusively expressed in the liver, and its product apoAV has a very low circulating concentration. New physiological roles of apoAV have been recently elucidated, such as control of chylomicron production in the intestine and TG accumulation in adipose tissue. The key role of APOA5 in TG metabolism has been largely shown through genetic studies in association with either severe or moderate hypertriglyceridemia. Studies suggest that APOA5 variants affect not only total TG concentrations but also the entire lipoprotein subclass distribution, shifting them toward atherogenic dyslipidemia in high-risk subjects. Environmental interactions and epigenetic factors are also crucial in regulating these processes. Delineation of the mechanisms involved in the transcriptional control of the gene, combined with determination of biological significance of the SNPs in the APOA5 locus, would help to fully understand the effect of APOA5 on TGs. In summary, APOA5 variants cause hypertriglyceridemia. In high cardiovascular risk patients (e.g., patients with metabolic syndrome or type 2 diabetes), APOA5 variants elevate TG levels and shift the entire lipoprotein subclass distribution toward atherogenic dyslipidemia. At a physiological level, apoAV seems to encompass more roles than those initially suggested after its discovery.
PURPOSE OF REVIEW: This review is intended to summarize the genetic studies published during the last 3 years that help us understand the physiology of apoAV and its clinical implications. RECENT FINDINGS:APOA5 is probably the gene with the strongest effect on triglyceride (TG) metabolism. APOA5 is almost exclusively expressed in the liver, and its product apoAV has a very low circulating concentration. New physiological roles of apoAV have been recently elucidated, such as control of chylomicron production in the intestine and TG accumulation in adipose tissue. The key role of APOA5 in TG metabolism has been largely shown through genetic studies in association with either severe or moderate hypertriglyceridemia. Studies suggest that APOA5 variants affect not only total TG concentrations but also the entire lipoprotein subclass distribution, shifting them toward atherogenic dyslipidemia in high-risk subjects. Environmental interactions and epigenetic factors are also crucial in regulating these processes. Delineation of the mechanisms involved in the transcriptional control of the gene, combined with determination of biological significance of the SNPs in the APOA5 locus, would help to fully understand the effect of APOA5 on TGs. In summary, APOA5 variants cause hypertriglyceridemia. In high cardiovascular risk patients (e.g., patients with metabolic syndrome or type 2 diabetes), APOA5 variants elevate TG levels and shift the entire lipoprotein subclass distribution toward atherogenic dyslipidemia. At a physiological level, apoAV seems to encompass more roles than those initially suggested after its discovery.
Authors: Cara L Carty; Samsiddhi Bhattacharjee; Jeff Haessler; Iona Cheng; Lucia A Hindorff; Vanita Aroda; Christopher S Carlson; Chun-Nan Hsu; Lynne Wilkens; Simin Liu; Elizabeth Selvin; Rebecca Jackson; Kari E North; Ulrike Peters; James S Pankow; Nilanjan Chatterjee; Charles Kooperberg Journal: Circ Cardiovasc Genet Date: 2014-07-14
Authors: H N van der Vliet; M G Sammels; A C Leegwater; J H Levels; P H Reitsma; W Boers; R A Chamuleau Journal: J Biol Chem Date: 2001-09-27 Impact factor: 5.157
Authors: E Danese; A M Minicozzi; M Benati; M Montagnana; E Paviati; G L Salvagno; M Gusella; F Pasini; G C Guidi; G Lippi Journal: Br J Cancer Date: 2013-07-09 Impact factor: 7.640