Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence

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.

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

“…The CYP2C9 variants are worth investigating since this member of the cytochrome P450 family has a major role in the metabolism of most statins and has more than 60 reported genetic variants [ 35 ]. Moreover, we observed in both cohorts an association between higher HDL-C and the minor alleles of rs1532624 and rs708272 SNPs of CETP, a protein involved in the transfer of cholesteryl esters from HDL-C to other lipoproteins [ 36 ], confirming the results of several studies performed on a multitude of different ethnicities [ 37 , 38 ].…”

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet

“…Thus, APOE4 carriers, despite their sensitivity to omega-3 deficiencies, may not always benefit from fish oil supplementation. Furthermore, Abdullah et al (2021), after reviewing the available literature, have recently shown APOE to be among the genes involved in the inter-individual variability of circulating cholesterol concentrations in response to diet (Abdullah et al 2021). Some more evidence of the impact of APOE genotype status on the response to diet comes from transgenic targeted gene replacement mice.…”

The integrative panel of fatty acid desaturase-2 (FADS2) rs174583 gene polymorphism and dietary indices (DQI-I and HEI) affects cardiovascular risk factors among obese individuals

“…Genome wide association studies (GWAS) have paved the way for identification of Single nucleotide polymorphisms (SNPs) as drivers of cardiometabolic diseases. Therefore, SNPs have been known as a proper choice to identify phenotypic differences and address inter-individual variability [ 14 ]. In this regard, it is of great importance to identify SNP in the fatty acid desaturase (FADS) genes and determine their interaction with environmental factors such as diet in relation to risk of metabolic diseases.…”