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D Gaudet

Publications and source records attributed to D Gaudet.

43 records · Page 3Linked to original sources
PubMed1995

Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by elevated plasma concentrations of LDL cholesterol resulting from mutations in the gene for the LDL receptor. Low HDL cholesterol levels are seen frequently in patients both heterozygous and homozygous for mutations in this gene. Suggested mechanisms for reduced HDL levels in FH patients have been altered apolipoprotein A-1 metabolism and elevated cholesteryl ester transfer protein activity, but the molecular basis for hypoalphalipoproteinemia in any of these patients has not yet been identified. We investigated four large families in which individuals were found to be double heterozygotes for both FH and lipoprotein lipase (LPL) deficiency. These double heterozygotes have significantly less HDL cholesterol than persons with FH or LPL heterozygosity alone. In the double heterozygotes, HDL particle composition is not significantly different from FH heterozygotes, suggesting a quantitative rather than qualitative defect in HDL metabolism in these persons. We propose that mutations in the LPL gene may be a cause of low HDL cholesterol levels in some individuals heterozygous for FH.

Adult↗
PubMed1989

Hypertriglyceridemia and lower LDL cholesterol concentration in relation to apolipoprotein E phenotypes in myotonic dystrophy.

Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors.

Adolescent↗
PubMed1989

Myotonic dystrophy: linkage with apolipoprotein E and estimation of the gene carrier status with genetic markers.

The genes for myotonic dystrophy (MD) and for apolipoprotein E (ApoE) belong to a chromosome 19 synthenic group of markers. A familial linkage analysis between MD and ApoE was performed using the J Ott LIPED program (IBM PC/XT, April 1984) to estimate the genetic distance between these 2 genes. Of a total of 136 individuals in 11 MD families, 81 were confirmed to be affected by the disease and 41 were asymptomatic. ApoE phenotypes were determined in 115 of these 122 individuals. No recombinant was observed out of 74 meioses which were informatives for both MD and the ApoE isoproteins. A global maximal lod score Z of 19.00 was obtained at the recombination fraction theta = 0. The upper theta value at the confidence interval corresponding to the peak lod score (Z max) - 1 was 0.03. This suggests that the loci for MD and ApoE are at a distance of 0 to 0.03 Morgan. Since ApoE and apolipoprotein C2 (ApoC2) have been shown by others to be about 40 kb apart, our data are therefore consistent with the distance estimate of 0.02 Morgan reported between MD and ApoC2. The D19S19 (LDR152) polymorphic DNA sequence is also tightly linked to MD on chromosome 19. The segregation of ApoE isoproteins and of ApoC2 and D19S19 DNA polymorphism was utilized for evaluating the probability for individuals at risk of inheriting the disease gene in MD families. Data are presented on 3 families to emphasize the usefulness of genetic markers to estimate the MD gene carrier status of asymptomatic individuals and also for those presenting a partial syndrome. The limitations of such approach are also discussed.

Apolipoproteins E↗
PubMed1982

Importance of subtyping in psychopharmacogenetic studies.

Research on the importance of genetic and environmental risk factors (multifactorial) in the etiology of mental disorders and substance use disorders (alcoholism) is now growing rapidly. Biological and psychological studies in this field should include basic concepts of medical genetics and take heterogeneity (multidimensionality) of mental disorders into account. One of the best means to cope with heterogeneity is to redefine the diagnostic phenotype at different levels: biochemical, behavioral, familial. Data are presented where the introduction of different quantitative definitions of the phenotype and their analysis by multivariate technics are used for better understanding of alcoholic disorders.

Alcoholism↗