Apolipoprotein E polymorphism and plasma cholesterol response to probucol

Probucol has been shown to be an effective and well-tolerated cholesterol-lowering drug. However, response in terms of cholesterol reduction has been shown to vary significantly among individuals. The purpose of this study was to assess the role of apolipoprotein E polymorphism in determining this variation. A retrospective study of 89 hypercholesterolemic type II patients who had been treated with probucol (1 g/d) and for whom the apolipoprotein E phenotype was known was carried out. The patients were first grouped into those with heterozygous familial hypercholesterolemia (FH) and those considered to have other forms of hypercholesterolemia (non-FH). Further subclassification of the individuals in both groups as IIa or IIb, allowed the definition of four diagnostic classes, FH IIa or IIb and non-FH IIa or IIb. Among these classes there was no significant heterogeneity for the relationship between response and age or sex. After correction for between-class heterogeneity in duration of probucol treatment, comparison of individuals with the apo E3/3 phenotype with those carrying the [epsilon]4 allele showed significant differences in cholesterol reduction both absolute change and percent change. Further contrasts between diagnostic and apo E genotype stratifications of these data showed that the FH patients carrying the [epsilon]4 allele had the greatest reduction in cholesterol level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26631/1/0000172.pd

The use of measured genotype information in the analysis of quantitative phenotypes in man.

We have begun a measured genotype approach to the genetic analysis of lipid and lipoprotein variability. This approach enables one to simultaneously estimate the frequencies and effects of alleles at specific loci along with the residual polygenetic variance component. In this study we consider the contribution of three common alleles at the locus coding for apolipoprotein E to interindividual variation of total cholesterol, betalipoprotein, and triglyceride levels. A sample of 102 nuclear families consisting of 434 individuals was studied. The frequencies of the ε2, ε3, and ε4 alleles in this sample are 0·137,0·740, and 0·123, respectively. In separate analyses of cholesterol and betalipoprotein levels, a complete model that includes the effects of the six apo E genotypes, unmeasured polygenes, and individual specific environmental effects fits these data significantly better than a reduced model that does not include the effects of the apo E polymorphism or a reduced model that does not include the effects of polygenes. On the average the ε2 allele lowers total cholesterol and betalipoprotein levels by 0·425 mmol/l and 0·811 units, respectively. The ε4 allele is associated with an average increase of these phenotypes by 0·255 mmol/l and 0·628 units, respectively. Simultaneous estimates of the interindividual variability of total cholesterol levels attributable to the apo E polymorphism and to residual polygenic effects are 8% and 56%, respectively. For betalipoprotein levels, we simultaneously estimate these values to be 7% and 42%, respectively. A reduced model including the effects of polygenes but not the effects of the apo E polymorphism fitted the triglyceride data as well as the complete model. The estimate of the fraction of interindividual variability associated with polygenetic effects was 26.5%. We review our present understanding of the genetic architecture underlying variability of cholesterol levels in the population at large and infer that the majority of the genetic variability may be accounted for by polymorphic gene loci with moderate effects on cholesterol levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65212/1/j.1469-1809.1987.tb00874.x.pd

Accounting for information: Information and knowledge in the annual reports of FTSE 100 companies

The purpose of this study was to assess the ways in which a sample group of companies discuss information and knowledge. Quantitative and qualitative content analyses were used to survey the way that companies present and value information and knowledge, based on the annual reports of the FTSE 100, the United Kingdom's largest publicly-listed companies. A novel content analysis approach is used, based on a set of categories proposed by Oppenheim, Stenson and Wilson. Many of the companies analysed made explicit the importance of information and knowledge, through either discussion in the text of the annual report or through an attempt to assign a monetary value to information assets. Where the importance of information and knowledge was not made explicit, the study revealed links between successful performance and effective use of information assets. Different categories of information assets were identified within the annual reports. Conclusions drawn from the analysis include that information and knowledge are demonstrably important to FTSE 100 companies, although the specific term “knowledge” does not appear to have a special significance in the companies’ lexicon; and that certain sectors, such as General Financial, General Retail, Travel & Leisure, Mining, Aerospace & Defence and Software & Computer Services, mention information and knowledge more than others