Review
Influence of genetic factors in the modulation of postprandial lipemia

https://doi.org/10.1016/j.atherosclerosissup.2008.05.005Get rights and content

Abstract

Postprandial lipemia is traditionally defined by the extent and duration of the increase in plasma triglycerides in response to a fat-enriched meal. The relationship between alimentary lipemia and coronary disease is of great interest in view of the epidemiological and experimental evidence that underlies it. The rate of synthesis of triglyceride-rich lipoproteins, lipoprotein lipase-mediated triglyceride hydrolysis, and the hepatic capture of chylomicron remnants via the interaction of the lipoprotein receptor with APOE and LPL, are the fundamental pillars of the metabolism and modification of these lipoproteins. The modulation of such phenomena is influenced by both genetic and environmental factors, thus explaining their extraordinary individual variance. This review presents the current evidence linking a number of candidate genes to the modulation of postprandial lipid metabolism.

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

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