ReviewInfluence of genetic factors in the modulation of postprandial lipemia
Introduction
Despite the completion of the Human Genome Project a few years ago, the knowledge of the genes involved in cardiovascular disease (CVD) risk remains incomplete. Plasma lipid levels are one of the best well-established risk factors for CVD. Therefore, it is of particular interest to identify the most relevant genes for lipid metabolism and characterize their interactions with other genes and environmental factors. Most of the past and current work in this direction has been carried out using blood samples obtained in the fasting state. Whereas, this is optimal for standardization purposes, fasting is not the typical physiological state of the modern human being, which spends most the time in the postprandial state. Therefore, the assessment of the postprandial lipemic response may be more relevant to identify disturbances in lipid metabolism than measures taken in the fasting state.
Plasma lipoproteins undergo a series of changes in their composition and concentration during the postprandial period. The capacity of the individual to respond adequately to dietary fat, i.e. its capacity to efficiently catabolise the dietary triglycerides (TG) that accumulate during the postprandial period, determines the ability to return to proper homeostasis. The rate of synthesis of triglyceride-rich lipoproteins (TRL), their lipoprotein lipase (LPL)-mediated hydrolysis, and the hepatic capture of chylomicron remnants via the interaction of the lipoprotein receptor (LPR) with APOE and LPL, are the known basis of TRL metabolism. Moreover, their modulation by genetic or environmental conditions explains the dramatic individual variability observed in the postprandial lipemic response. It is of great interest to survey the existing scientific evidence that relates this variability to such factors as the genetic substrate, the environment, the physiological factors and the pathological conditions that modify the metabolism during the postprandial period.
Section snippets
Genetic polymorphisms and postprandial lipemia
Most of these studies carried out during the past decade have been restricted to examining single-nucleotide polymorphisms (SNPs) at individual genes for their relation with specific traits. More recently this approach has been extended to the study of combination of alleles that tend to be transmitted in conjunction (haplotypes), and that can provide better information about the architecture of the genes under consideration. The increasing body of data is also providing a better understanding
Conclusions
Both genetic and environmental factors appear to influence the modulation of postprandial lipoprotein metabolism. However, the magnitude of the genetic influence is not precisely known. Despite this caveat substantial effort has been placed in the study of candidate genes involved in fasting lipid metabolism. Most of the genes examined (APOA1, APOE, APOB, APOC1, APOC3, APOA4, APOA5, LPL, LH, FABP2, FATP, MTP, SRB1, PPARG and PLIN) have shown significant associations; however, we need to keep in
Conflict of interest
None.
Acknowledgements
This work was supported by research grants from NIH/NHLBI grant no. HL54776 and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service and by CIBER (CBO/6/03), Instituto de Salud Carlos III; CICYT (SAF 01/2466-C05 04 to F P-J, SAF 01/0366 to J L-M, AGL 2004-07907 to J L-M, AGL 2006-01979 to JL-M), the Spanish Ministry of Health (FIS 01/0449, FIS PI041619 to CM); Fundación Cultural “Hospital Reina Sofía-Cajasur”; Consejería de Salud, Servicio Andaluz de
References (54)
- et al.
Effects of the human apolipoprotein A-I promoter G-A mutation on postprandial lipoprotein metabolism
Am J Clin Nutr
(2002) - et al.
Overexpression of human apolipoprotein A-II in mice induces hypertriglyceridemia due to defective very low density lipoprotein hydrolysis
J Biol Chem
(1999) - et al.
Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV
J Biol Chem
(1990) - et al.
The apolipoprotein A-IV-360 His polymorphism determines the dietary fat clearance in normal subjects
Atherosclerosis
(2000) - et al.
Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus
J Lipid Res
(1998) - et al.
Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges
Bochim Biophys Acta
(2003) - et al.
Genetic analysis of a polymorphism in the human apolipoprotein A-V gene: effect on plasma lipids
J Lipid Res
(2003) - et al.
A single nucleotide polymorphism of the apolipoprotein A-V gene −1131T > C modulates postprandial lipoprotein metabolism
Atherosclerosis
(2006) - et al.
Association of apolipoprotein A5 variants with LDL particle size and triacylglycerol in Japanese Americans
Biochim Biophys Acta
(2004) - et al.
Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease
Atherosclerosis
(2004)
Analysis of the human apolipoprotein B gene; complete structure of the B-74 region
Gene
Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster
J Lipid Res
The influence of the apolipoprotein E gene promoter (219G/T) polymorphism on postprandial lipoprotein metabolism in young normolipemic males
J Lipid Res
Intestinal fatty acid binding protein polymorphism at codon 54 is not associated with postprandial responses to fat and glucose tolerance tests in healthy young Europeans. Results from EARS II participants
Atherosclerosis
Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested
Am J Clin Nutr
A common polymorphism in the fatty acid transport protein-1 gene associated with elevated post-prandial lipaemia and alterations in LDL particle size distribution
Atherosclerosis
Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency
J Lipid Res
LPL promoter −93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics
J Lipid Res
Influence of the −514C/T polymorphism in the promoter of the hepatic lipase gene on postprandial lipoprotein metabolism
Atherosclerosis
Expression cloning of SR-BI, a CD36-related class B scavenger receptor
J Biol Chem
Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1
J Biol Chem
Scavenger receptor class B Type I (SCARB1) c 1119C > T polymorphism affects postprandial triglyceride metabolism in men
J Nutr
Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis
J Biol Chem
Postprandial triacylglycerol metabolism is modified by the presence of genetic variation at the perilipin (PLIN) locus in 2 white populations
Am J Clin Nutr
Increased postprandial lipemia in Apo A-IMilano carriers
Arterioscler Thromb
Human evidence that the apolipoprotein a-II gene is implicated in visceral fat accumulation and metabolism of triglyceride-rich lipoproteins
Circulation
An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing
Science
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