👤 Patrick Borel

Lutein (L) and zeaxanthin (Z) are involved in visual function and could prevent age-related macular degeneration and chronic diseases and improve cognitive performances. Adipose tissue is the main storage site for these xanthophylls (Xanth). The factors affecting their concentrations in this tissue remain poorly understood but in animal models, genetic variations in apolipoprotein E and β-carotene oxygenase 2 have been associated with adipose tissue L concentration. Therefore, the aims of this study were to better characterize the interindividual variability of adipose tissue Xanth concentration and to identify single nucleotide polymorphisms (SNPs) associated with it. Periumbilical subcutaneous adipose tissue samples were collected on 6 occasions in 42 healthy adult males and L and Z concentrations were measured by HPLC. Participants had their whole genome genotyped and the associations of 3589 SNPs in 49 candidate genes with the concentrations of L and Z were measured. Mean L and Z concentrations were 281 ± 27 and 150 ± 14 nmol g Show less

Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, β-carotene or lycopene. Several studies suggest its bioavailability displays an elevated interindividual variability. The aim of this work is to investigate whether a combination of SNPs is associated with this variability. Thirty-seven healthy adult males consume a test meal that provides phytofluene from a tomato puree. Phytofluene concentrations are measured at fast and in chylomicrons at regular time intervals after meal intake. Identification of the combination of SNPs that best explained the interindividual variability of the phytofluene response is assessed by partial least squares regression. There is a large interindividual variability in the phytofluene response, with CV = 88%. Phytofluene bioavailability is positively correlated with fasting plasma phytofluene concentration (r = 0.57; p = 2 × 10 This study reports a combination of SNPs that is associated with a significant part of the interindividual variability of phytofluene bioavailability in a healthy male adult population. Show less

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

The PICALM-MLLT10 fusion gene, generated by the t(10;11)(p12-13;q14-21) translocation, is a rare but recurrent event in acute leukemias. In this study, we assessed the characteristics and outcome of 18 PICALM-MLLT10 AML patients. As compared with non PICALM-MLLT10 patients (n=72), PICALM-MLLT10 AML were characterized by more frequent extramedullary diseases, CD7 expression and higher platelet counts. Three out of four therapy-related PICALM-MLLT10 AMLs had been previously treated for diffuse large B-cell lymphoma. The complete response rate was 71% after intensive chemotherapy. PICALM-MLLT10 patients had a shorter median overall survival than patients with favorable cytogenetics (12 months vs. not reached, p=0.07) but not significantly different from those of intermediate (26 months, p=0.32) or unfavorable cytogenetic groups (8 months, p=0.13). Long term responses were achieved in a subset of patients after allogeneic stem-cell transplantation but also after high-dose cytarabine. 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