Search PubMed⌕ Search

Biomedical subjects

T D Dyer

Publications and source records attributed to T D Dyer.

24 records · Page 2Linked to original sources
PubMed1995

Genetic control of apolipoprotein A-I distribution among HDL subclasses.

We conducted genetic analyses to determine the components of variation for size distributions of apolipoprotein (apo) A-I among human plasma lipoproteins resolved on the basis of size. Analyses used data for 717 individuals in 26 pedigrees. Apo A-I distributions among lipoprotein size classes were measured by nondenaturing gradient gel electrophoresis (GGE) and immunoblotting procedures. Curves were fitted to apo A-I absorbance profiles to estimate fractional absorbance in each of five high-density lipoprotein (HDL) subclasses. Multivariate regression analyses revealed several covariates (sex, age, diabetes, and apo A-I concentrations) that were significantly associated with variation in one or more HDL subclasses. Female gender and elevated apo A-I concentrations were associated with increases in proportion of apo A-I in larger HDLs, while increasing age and diabetes were associated with decreases. The analyses showed significant heritabilities. h2, for each variable representing the different HDL subclasses. Both genetic and nongenetic effects on apo A-I size distributions were generally exerted across the range of lipoprotein sizes, as suggested by high genetic and environmental correlations between HDL subclass variables. Decomposition of total overall variance showed that unidentified environmental factors accounted for 48% of variation in apo A-I size distribution, while genetic factors explained about 36% and the identified covariates explained the remaining 16%. When considered separately, apo A-I concentration explained only 5% of the total variation in apo A-I size distribution, indicating that apo A-I concentration is a poor predictor of apo A-I size distribution. In summary, the data suggest that there are significant genetic and environmental effects on apo A-I size distribution in humans, and that they are general metabolic effects rather than effects on specific HDL subclasses.

Adult↗
PubMed1995

Effect of diabetes on lipoprotein size.

The effects of diabetes on lipoprotein particle sizes were assessed using samples from 94 subjects with non-insulin-dependent diabetes mellitus. From a larger population of nondiabetic subjects who showed normal glucose tolerance, we selected an exact match in terms of age, sex, and menopausal status. We designed a protocol to make nondenaturing gradient gels for the resolution of LDL subfractions and generated two measures of LDL size: diameter of the predominant LDL species and proportion of LDL cholesterol (LDL-C) in particles larger than 25.5 nm (large LDL-C). Similarly, we made two measures of HDL size, large HDL cholesterol (HDL-C) and large HDL-apoAI, which represents the proportion of HDL-C and apoAI, respectively, occurring on particles larger than HDL-3. In pairwise comparisons, diabetes was associated with significantly (P < .004) smaller lipoprotein particles for all measures except large HDL-C. Each of the size measures was significantly and positively correlated with each of the others, suggesting that common metabolic mechanisms influence lipoprotein particle sizes across classes of lipoproteins. In addition, each of the size measures was correlated with a variety of measures of HDL and beta-lipoprotein concentrations, which included HDL-C, LDL-C, triglycerides, and apoAI, apoB, and apoE. We used stepwise regression analyses to select from the measures of lipoprotein concentrations those independently correlated with each of the lipoprotein size measures. After adjusting for these metabolic correlates of lipoprotein size measures, we found the effect of diabetes on lipoprotein size measures was no longer significant except for a modest effect (P = .027) on large HDL-apoAI.

Adult↗
PubMed1994

Apolipoprotein B and a second major gene locus contribute to phenotypic variation of spontaneous hypercholesterolemia in pigs.

The Lpb5 apolipoprotein B (apoB) allele occurs in pigs with spontaneous hypercholesterolemia. Low-density lipoprotein (LDL) from these pigs binds to the LDL receptor with a lower affinity and is cleared from the circulation more slowly than control pig LDL. However, the severity of hypercholesterolemia in pigs with the mutant apoB allele is highly variable. This study aimed to determine the metabolic basis for the phenotypic heterogeneity among Lpb5 pigs. Lpb5 pigs were divided into two groups: those with plasma cholesterol greater than 180 mg/dL (Lpb5.1) and those with plasma cholesterol less than 180 mg/dL (Lpb5.2). LDL from both Lpb5.1 and Lpb5.2 pigs was catabolized in vivo and in vitro at a similarly reduced rate. The difference in plasma cholesterol between the two phenotypic groups was in part due to a higher buoyant LDL production rate in Lpb5.1 pigs than in Lpb5.2 pigs. The in vivo LDL receptor status was evaluated by measuring the catabolism of LDL chemically modified to abrogate LDL receptor binding. Approximately 50% of LDL clearance in normal and Lpb5.2 pigs was via the LDL receptor; in Lpb5.1 pigs, 100% of LDL clearance was LDL receptor independent. Quantitative pedigree analysis of the segregation of the plasma cholesterol phenotype suggested that two major gene loci (the apoB locus and a second apparently unlinked locus) contribute to the determination of plasma cholesterol levels in this pig population.

Animals↗
PubMed1990

Genetic analysis of apolipoprotein A-I in two dietary environments.

Although of great clinical and biological importance, the role of genotype-diet interaction in lipoprotein metabolism and atherosclerosis is still poorly understood. We analyzed serum apolipoprotein A-I (apo A-I) concentrations of approximately 600 pedigreed baboons that were fed two dietary regimens: (1) a basal diet and (2) an atherogenic (high-cholesterol, saturated-fat) diet. Complex segregation analysis was performed separately for apo A-I concentrations in each dietary environment. A major locus model with a recessive allele for high levels of apo A-I and a polygenic component best fit the family data for both diets. Using bivariate segregation analysis, we showed that the major genes detected in the univariate analyses represent two distinct loci that act additively to determine apo A-I concentrations. These two loci accounted for approximately 40% of the total phenotypic variance in apo A-I levels in each dietary environment and were also responsible for 33% of the variation in apo A-I response to the atherogenic diet. Both major loci were influenced by genotype-diet interaction in which the two-locus genotypes exhibited heterogeneous responses to the atherogenic diet. Most genotypes responded to the atherogenic diet with an increase in apo A-I, but two genotypes showed a decrease that can be traced to the effect of one of the major loci. The presence of two major loci and genotype-diet interaction may be responsible for the equivocal results obtained in human pedigree studies of apo A-I.

Animals↗