👤 Richard Planells

The postprandial chylomicron (CM) triacylglycerol (TG) response to dietary fat, which is positively associated with atherosclerosis and cardiovascular disease risk, displays a high interindividual variability. This is assumed to be due, at least partly, to polymorphisms in genes involved in lipid metabolism. Existing studies have focused on single nucleotide polymorphisms (SNPs), resulting in only a low explained variability. We aimed to identify a combination of SNPs associated with the postprandial CM TG response. Thirty-three healthy male volunteers were subjected to 4 standardized fat tolerance test meals (to correct for intraindividual variability) and genotyped using whole-genome microarrays. The plasma CM TG concentration was measured at regular interval times after each meal. The association of SNPs in or near candidate genes (126 genes representing 6225 SNPs) with the postprandial CM TG concentration (0-8 h areas under the curve averaged for the 4 test meals) was assessed by partial least squares regression, a multivariate statistical approach. Data obtained allowed us to generate a validated significant model (P = 1.3 × 10(-7)) that included 42 SNPs in 23 genes (ABCA1, APOA1, APOA5, APOB, BET1, CD36, COBLL1, ELOVL5, FRMD5, GPAM, INSIG2, IRS1, LDLR, LIPC, LPL, LYPLAL1, MC4R, NAT2, PARK2, SLC27A5, SLC27A6, TCF7L2, and ZNF664) and explained 88% of the variance. In 39 of these SNPs, univariate analysis showed that subjects with different genotypes exhibited significantly different (q < .05) postprandial CM TG responses. Using a multivariate approach, we report a combination of SNPs that explains a significant part of the variability in the postprandial CM TG response. Show less

Vitamin E and carotenoids are fat-soluble micronutrients carried by plasma lipoproteins. Their plasma concentrations are governed by several factors, some of which are genetic, but data on these genetic factors remain scarce. We hypothesized that genes involved in lipid metabolism, i.e. the genes implicated in intestinal uptake, intracellular trafficking, and the lipoprotein distribution of lipids, play a role in the plasma concentrations of these micronutrients. To verify this hypothesis, we assessed whether the plasma status of vitamin E and carotenoids is related to genes involved in lipid metabolism. Fasting plasma vitamin E (alpha- and gamma-tocopherol) and carotenoid (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, and zeaxanthin) concentrations were measured in 48 males and 80 females. The following genes were genotyped [single nucleotide polymorphisms (SNP)]: apolipoprotein (apo) A-IV, apo B, apo E, lipoprotein lipase, and scavenger-receptor class B type I (SR-BI). Plasma alpha-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV, apo E, and SR-BI. Plasma gamma-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and SR-BI. Alpha-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Beta-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in apo B and SR-BI. Lycopene concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and apo B. Beta-cryptoxanthin concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Plasma lutein and zeaxanthin concentrations did not differ in subjects bearing different SNP. Most of the differences remained significant after the plasma micronutrients were adjusted for plasma triglycerides and cholesterol. These results suggest that genes involved in lipid metabolism influence the plasma concentrations of these fat-soluble micronutrients. Show less

While human diets have markedly evolved since their origin, the human genome has only marginally changed. Nevertheless, polymorphisms of common genes are widespread. It has been substantiated that most major diseases (including cardiovascular disease, diabetes, obesity and cancers) result from the interaction between genetic susceptibility and environmental factors, including diet. In the field of lipoprotein metabolism and cardiovascular disease several gene polymorphisms for key proteins, such as apoproteins (apo) E, B, A-IV and C-III, LDL receptor, microsomal transfer protein (MTP), fatty acid-binding protein (FABP), cholesteryl ester transfer protein (CETP), lipoprotein lipase and hepatic lipase, have been identified and linked to variable responses to diets. We are carrying out an intervention study (RIVAGE) in Marseille dedicated to investigating the interactions between diets (Mediterranean or low-fat types v. standard Western type), risk factors for cardiovascular disease and gene polymorphisms in about 300 patients randomized into two groups over periods of 3 and 12 months. Some data obtained in about 100 patients after 3 months of dietary change are available. Among single nucleotide polymorphisms (SNP) already studied (apoE (epsilon2, epsilon3, epsilon4), apoB (-516C/T), apoC-III (SstI), apoA-IV (Ser347Thr), MTP (-493G/T), intestinal FABP (Ala54Thr), CETP (TaqIB) and hepatic lipase (-480C/T)), some SNP showed interactions with diets in relation to changes in particular variables after 3 months on the dietary regimens. This was the case for apoE and LDL-cholesterol and triacylglycerols, apoA-IV and LDL-cholesterol, MTP and LDL-cholesterol, intestinal FABP and triacylglycerols. These data provide evidence of the interaction between some SNP and the metabolic response to diets. Show less