Common genetic variations involved in the inter-individual variability of circulating cholesterol concentrations in response to diets: a narrative review of recent evidence

Authors: ABDULLAH, MOHAMMAD - Kuwait University; VAZQUEZ-VIDAL, ITZEL - University Of Manitoba; Baer, David; HOUSE, JAMES - University Of Manitoba; JONES, PETER - University Of Manitoba; DESMARCHELIER, CHARLES - Aix-Marseille University

Submitted to: Nutrients
Publication Type: Review Article
Publication Acceptance Date: 2/12/2021
Publication Date: 2/22/2021
Citation: Abdullah, M.M.H., Vazquez-Vidal, I., Baer, D.J., House, J.D., Jones, P.J.H., Desmarchelier, C. 2021. Common genetic variations involved in the inter-individual variability of circulating cholesterol concentrations in response to diets: a narrative review of recent evidence. Nutrients. 13(2):695-710. https://doi.org/10.3390/nu13020695.
DOI: https://doi.org/10.3390/nu13020695

Interpretive Summary: Personalized nutrition is the next frontier for food and health industries. Cardiovascular disease (CVD) is still a leading cause of death globally and it is estimated that 90% cases thereof are preventable, with diet considered as the first line of treatment. Lowering of blood cholesterol concentrations is a major target in both primary and secondary prevention of CVD but high interindividual variability exists in lipid level responses after a given dietary intervention. The number of studies dedicated to the identification of single nucleotide polymorphisms (SNPs - a form of genetic variation) modulating the response to dietary interventions with regard to blood lipid profile has increased considerably over the last few years. The objective of this review is to present the most recent and clinically relevant findings concerning the effect of gene-nutrient interactions on circulating cholesterol concentrations, established biomarkers of cardiovascular health. Some studies have also shown that combinations of SNPs could explain a higher proportion of the variability in response to various dietary interventions. Collectively, these studies show that the additive effect of several SNPs which, taken individually may have a small significant effect, could explain a significant part of the variability in response to a dietary intervention. Thus, these data show the advantage of complex analyses including combinatory patterns of SNPs compared to the low predictive value of single SNP approaches. Future research, including multi-side intervention trials, should be designed to explore combinatory patterns of genetic variability in order to better understand the impact of gene-diet interactions on serum lipid profiles.

Technical Abstract: The number of nutrigenetic studies dedicated to the identification of single nucleotide polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has increased considerably over the last decade. However, the robustness of the evidence-based science supporting the area remains to be evaluated. The objective of this review was to present recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol metabolism and transport, and dietary intakes or interventions on circulating cholesterol concentrations, which are causally involved in cardiovascular diseases and established biomarkers of cardiovascular health. We identified recent studies (2014–2020) that reported significant SNP–diet interactions in 14 cholesterol-related genes (NPC1L1, ABCA1, ABCG5, ABCG8, APOA1, APOA2, APOA5, APOB, APOE, CETP, CYP7A1, DHCR7, LPL, and LIPC), and which replicated associations observed in previous studies. Some studies have also shown that combinations of SNPs could explain a higher proportion of variability in response to dietary interventions. Although some findings still need replication, including in larger and more diverse study populations, there is good evidence that some SNPs are consistently associated with differing circulating cholesterol concentrations in response to dietary interventions. These results could help clinicians provide patients with more personalized dietary recommendations, in order to lower their risk for cardiovascular disease.