Quantitative differences in gene expression are thought to contribute to phenotypic differences between individuals. We generated genome-wide transcriptional profiles of lymphocyte samples from 1,240 participants in the San Antonio Family Heart Study. The expression levels of 85% of the 19,648 detected autosomal transcripts were significantly heritable. Linkage analysis uncovered >1,000 cis-regulated transcripts at a false discovery rate of 5% and showed that the expression quantitative trait loci with the most significant linkage evidence are often located at the structural locus of a given transcript. To highlight the usefulness of this much-enlarged map of cis-regulated transcripts for the discovery of genes that influence complex traits in humans, as an example we selected high-density lipoprotein cholesterol concentration as a phenotype of clinical importance, and identified the cis-regulated vanin 1 (VNN1) gene as harboring sequence variants that influence high-density lipoprotein cholesterol concentrations.

These results highlight the importance of considering genetic factors in studies of risk factors for cardiovascular disease.

Circulating chemerin levels were associated with metabolic syndrome phenotypes in a second, unrelated human population. This replicated result using a large human sample suggests that chemerin may be involved in the development of the metabolic syndrome.

Nondenaturing gradient gel electrophoresis continues to be used widely for resolution and characterization of lipoprotein subclasses. Methods for making such gels in the laboratory have been published, but occasionally samples do not display uniform mobilities for all lanes in a laboratory-made gel.To help overcome this limitation, we recommend a modification-addition of a sucrose gradient-that significantly improves within-gel variation in protein mobility. Extensive literature supports the hypothesis that knowledge of lipoprotein size distributions provides a more detailed indication of lipoprotein metabolism and a more accurate prediction of cardiovascular disease risk (1). Lipoprotein size distributions have been measured by a number of physicochemical methods, perhaps most commonly by gradient gel electrophoresis. Previously, we have described a highly reproducible method designed to make nondenaturing acrylamide gradient gels for the electrophoretic separation of plasma HDLs (2) and LDLs (3). More recently, we described a composite gradient gel that enabled the simultaneous analysis of both LDLs and HDLs (4). Estimates of peak diameter and fractional absorbance made from the composite gel were strongly correlated with those made using the respective dedicated gel formats (4). Recently, however, we began to notice that the gels have run unevenly on occasion; that is, samples appeared to run different distances depending on location in the gel (generally, samples in the outside lanes tended to run faster than those in the interior lanes, leading to a "frowning" appearance). The problem was observed in the LDL portion of the gradient and did not seem to affect mobilities of HDLs in the areas of higher acrylamide concentrations.In a previous study, Rhigetti et al. (5) reported that convective flows are imprinted in the final gel structure, but this effect can be minimized by use of a sucrose gradient during the gelling process. Accordingly, we modified our published protocol and tested whether the addition of a sucrose gradient might solve the problem of differential mobilities for different lanes in a gel.Composite acrylamide gradient gels were made exactly as described previously (4) except that, to some high limit solutions, we added sucrose (10 g/l). The two types of gels will be referred to as Ϫ sucrose and ϩ sucrose. Briefly, the gradient was made with two solutions: a low limit solution (3% acrylamide with 4% cross-linker) and a high limit solution (31% acrylamide with 5.5% cross-linker and Ϯ 10% sucrose). Gels were cast in groups of 16 and allowed to polymerize for 3 h prior to storage at 4 Њ C for no more than 1 month before use. Serum and plasma samples from baboons and humans, respectively, were subjected to electrophoresis at 3,000 v · h (using electrophoresis chambers supplied by CBS Scientific) and staining with Sudan black B. These samples were run as part of ongoing studies in this laboratory. Following restoration of the original gel shape and size in the electrophoresis buffer, we su...

Phytosterol-supplemented ground beef effectively lowers plasma TC and LDL cholesterol and has the potential to become a functional food to help reduce the risk of cardiovascular disease.