Genetic variation and the lipid response to dietary intervention: a systematic review

Abstract

There is wide interindividual variation in the lipid and lipoprotein responses to dietary change, and the existence of consistent hypo- and hyperresponders supports the hypothesis that responsiveness is related to genetic variation. Many studies have investigated the possibility that the heterogeneity in responsiveness to changes in dietary fat, cholesterol, and fiber intake is explained by variation in genes whose products affect lipoprotein metabolism, eg, apolipoproteins, enzymes, and receptors. A systematic review of the literature was carried out to investigate the effect of genetic variation on the lipid response to dietary intervention. A search strategy for the MEDLINE database retrieved 2540 articles from 1966 to February 2002. This strategy was adapted and performed on the EMBASE database, which retrieved 2473 articles from 1980 to week 9, 2002. Reference lists from relevant journal articles were also checked. This is the first systematic review of the literature, and it summarizes results available from 74 relevant articles. There is evidence to suggest that variation in the genes for apolipoprotein (apo) A-I, apo A-IV, apo B, and apo E contributes to the heterogeneity in the lipid response to dietary intervention. However, the effects of genetic variation are not consistently seen and are sometimes conflicting. Future studies need to have much larger sample sizes based on power calculations and carefully controlled dietary interventions and should investigate the effects of polymorphisms in multiple genes instead of the effects of polymorphisms in single genes.

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

“…Responsiveness to dietary fat manipulation is recognised to be highly variable, with genetic variability known to be partly responsible. The systematic review by Masson et al (2003) includes studies that have examined the impact of genotype on the responsiveness of fasting lipids to dietary cholesterol (fifteen individual studies) and total fat or fatty acid composition (thirty-six individual studies; mainly manipulation of SFA, MUFA and PUFA ratios). Three of the cholesterol-manipulation studies have reported a greater circulating cholesterol response in E4 carriers.…”

“…Three of the cholesterol-manipulation studies have reported a greater circulating cholesterol response in E4 carriers. Eleven of the studies that manipulated dietary fat have demonstrated a genotype · treatment interaction, with the E4 subgroup being generally the most responsive (Masson et al 2003). For example, in the Schaefer et al (1997) study (n 148) a National Cholesterol Education Program…”

“…In the male participants, but not in the female participants, an E4 genotype was shown to be associated with greater LDLC reductions. In the systematic review (Masson et al 2003) the lack of significance reported in many of the studies is likely to be attributable to a lack of power to detect an inter-genotype difference in response, rather than a lack of a 'real' biological effect of apoE genotype. Many of the studies included cohorts of less than fifty participants and retrospective apoE genotype profiling, which often resulted in small group sizes in the rare allele groups.…”

Obesity and type 2 diabetes in Northern Canada's remote First Nations communities: the dietary dilemma

“…49 Again, this FABP2 Ala54Thr polymorphism was shown to modify the association between dietary saturated fat intake and lipid cholesterol concentrations as well as markers of insulin resistance in the Italian population. 49 Published reviews of gene-diet interactions clearly show that dietary factors modify the predisposing or protective effect of gene loci 50 and that the effect varies between populations. 43,50 To our knowledge, gene-environment interactions have never been studied in Northern First Nations populations.…”

APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a three-month primary intervention study targeted to reduce fat intake

“…This led to the emerging concept that such variable metabolic responses might derive from interactions between the individual's genetic background and dietary factors [27,46]. In that line, the variability of response would thereby result, at least in part, from the presence of allelic variants in the genes coding for proteins involved in the intermediary metabolism such as apolipoproteins, lipid-processing enzymes, lipid transfer proteins and receptors binding lipoproteins [24,41].…”