Linkage disequilibrium patterns and tagSNP transferability among European populations

The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of approximately 2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.     

Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (Type IIb) patients

Lowering high cholesterol concentration decreases the probability of atherosclerotic-related pathology onset. MUFA and PUFA decrease total plasma and LDL cholesterol but PUFA may increase the susceptibility of LDL to undergo oxidative modifications thus becoming more atherogenetic. Olive oil, the predominant fat source in Mediterranean diet, may combine the advantages of both lowering cholesterol level and decreasing LDL susceptibility to oxidation. We studied the effects of feeding MUFA vs PUFA enriched diet on LDL composition and feature in hypercholesterolemic (IIb) patients Antioxidant values remained constant during the study while LDL fatty acids composition reflected the dietary intake: MUFA concentration increased 11% whereas PUFA decreased 10% after olive oil diet (p < 0.05). PUFA/MUFA ratio and the unsaturation index were lower at the end of MUFA-enriched diet. The challenge, in vitro, of oleate-enriched LDL with Cu²⁺ yielded to lower lag-phase (p < 0.05) in diene conjugated production; the same LDL gave lower lipid hydroperoxide contents after exposition to AAPH. We conclude that oleate-enriched LDL and with lower PUFA content were more resistant to oxidative modifications, as measured by different peroxidation indexes. This feature acquired with the diet may be an useful tool for lowering LDL oxidation and indirectly their atherogenicity.     

IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection

Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection.